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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis

Author(s): Bedaballi Dey, Arvind Kumar and Anant Bahadur Patel*

Volume 22, Issue 11, 2024

Published on: 24 August, 2023

Page: [1778 - 1806] Pages: 29

DOI: 10.2174/1570159X21666230824091601

Price: $65

Abstract

Amyotrophic Lateral Sclerosis (ALS) is the most common, adult-onset, progressive motor neurodegenerative disorder that results in death within 3 years of the clinical diagnosis. Due to the clinicopathological heterogeneity, any reliable biomarkers for diagnosis or prognosis of ALS have not been identified till date. Moreover, the only three clinically approved treatments are not uniformly effective in slowing the disease progression. Over the last 15 years, there has been a rapid advancement in research on the complex pathomechanistic landscape of ALS that has opened up new avenues for successful clinical translation of targeted therapeutics. Multiple studies suggest that the age-dependent interaction of risk-associated genes with environmental factors and endogenous modifiers is critical to the multi-step process of ALS pathogenesis. In this review, we provide an updated discussion on the dysregulated cross-talk between intracellular homeostasis processes, the unique molecular networks across selectively vulnerable cell types, and the multisystemic nature of ALS pathomechanisms. Importantly, this work highlights the alteration in epigenetic and epitranscriptomic landscape due to gene-environment interactions, which have been largely overlooked in the context of ALS pathology. Finally, we suggest that precision medicine research in ALS will be largely benefitted from the stratification of patient groups based on the clinical phenotype, onset and progression, genome, exposome, and metabolic identities.

Keywords: Amyotrophic lateral sclerosis (ALS), motor neuron disease, pathophysiology, gene environment interaction, heterogeneity, metabolism, epigenetics, RNA modification.

Graphical Abstract
[1]
Checkoway, H.; Lundin, J.I.; Kelada, S.N. Neurodegenerative diseases. IARC Sci. Publ., 2011, (163), 407-419.
[PMID: 22997874]
[2]
Logroscino, G.; Piccininni, M.; Marin, B.; Nichols, E.; Abd-Allah, F.; Abdelalim, A.; Alahdab, F.; Asgedom, S.W.; Awasthi, A.; Chaiah, Y.; Daryani, A.; Do, H.P.; Dubey, M.; Elbaz, A.; Eskandarieh, S.; Farhadi, F.; Farzadfar, F.; Fereshtehnejad, S-M.; Fernandes, E.; Filip, I.; Foreman, K.J.; Gebre, A.K.; Gnedovskaya, E.V.; Hamidi, S.; Hay, S.I.; Irvani, S.S.N.; Ji, J.S.; Kasaeian, A.; Kim, Y.J.; Mantovani, L.G.; Mashamba-Thompson, T.P.; Mehndiratta, M.M.; Mokdad, A.H.; Nagel, G.; Nguyen, T.H.; Nixon, M.R.; Olagunju, A.T.; Owolabi, M.O.; Piradov, M.A.; Qorbani, M.; Radfar, A.; Reiner, R.C.; Sahraian, M.A.; Sarvi, S.; Sharif, M.; Temsah, O.; Tran, B.X.; Truong, N.T.; Venketasubramanian, N.; Winkler, A.S.; Yimer, E.M.; Feigin, V.L.; Vos, T.; Murray, C.J.L. Global, regional, and national burden of motor neuron diseases 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 2018, 17(12), 1083-1097.
[http://dx.doi.org/10.1016/S1474-4422(18)30404-6] [PMID: 30409709]
[3]
Longinetti, E.; Fang, F. Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Curr. Opin. Neurol., 2019, 32(5), 771-776.
[http://dx.doi.org/10.1097/WCO.0000000000000730] [PMID: 31361627]
[4]
Grad, L.I.; Rouleau, G.A.; Ravits, J.; Cashman, N.R. Clinical spectrum of amyotrophic lateral sclerosis (ALS). Cold Spring Harb. Perspect. Med., 2017, 7(8), a024117.
[http://dx.doi.org/10.1101/cshperspect.a024117] [PMID: 28003278]
[5]
Abramzon, Y.A.; Fratta, P.; Traynor, B.J.; Chia, R. The overlapping genetics of amyotrophic lateral sclerosis and frontotemporal dementia. Front. Neurosci., 2020, 14, 42.
[http://dx.doi.org/10.3389/fnins.2020.00042] [PMID: 32116499]
[6]
Masrori, P.; Van Damme, P. Amyotrophic lateral sclerosis: A clinical review. Eur. J. Neurol., 2020, 27(10), 1918-1929.
[http://dx.doi.org/10.1111/ene.14393] [PMID: 32526057]
[7]
Ferraiuolo, L.; Kirby, J.; Grierson, A.J.; Sendtner, M.; Shaw, P.J. Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat. Rev. Neurol., 2011, 7(11), 616-630.
[http://dx.doi.org/10.1038/nrneurol.2011.152] [PMID: 22051914]
[8]
Manjaly, Z.R.; Scott, K.M.; Abhinav, K.; Wijesekera, L.; Ganesalingam, J.; Goldstein, L.H.; Janssen, A.; Dougherty, A.; Willey, E.; Stanton, B.R.; Turner, M.R.; Ampong, M.A.; Sakel, M.; Orrell, R.W.; Howard, R.; Shaw, C.E.; Leigh, P.N.; Al-Chalabi, A. The sex ratio in amyotrophic lateral sclerosis: A population based study. Amyotroph. Lateral Scler., 2010, 11(5), 439-442.
[http://dx.doi.org/10.3109/17482961003610853] [PMID: 20225930]
[9]
Palese, F.; Sartori, A.; Verriello, L.; Ros, S.; Passadore, P.; Manganotti, P.; Barbone, F.; Pisa, F.E. Epidemiology of amyotrophic lateral sclerosis in Friuli-Venezia Giulia, North-Eastern Italy, 2002–2014: A retrospective population-based study. Amyotroph. Lateral Scler. Frontotemporal Degener., 2019, 20(1-2), 90-99.
[http://dx.doi.org/10.1080/21678421.2018.1511732] [PMID: 30430867]
[10]
Leighton, D.J.; Newton, J.; Stephenson, L.J.; Colville, S.; Davenport, R.; Gorrie, G.; Morrison, I.; Swingler, R.; Chandran, S.; Pal, S. Changing epidemiology of motor neurone disease in Scotland. J. Neurol., 2019, 266(4), 817-825.
[http://dx.doi.org/10.1007/s00415-019-09190-7] [PMID: 30805795]
[11]
Chiò, A.; Logroscino, G.; Traynor, B.J.; Collins, J.; Simeone, J.C.; Goldstein, L.A.; White, L.A. Global epidemiology of amyotrophic lateral sclerosis: A systematic review of the published literature. Neuroepidemiology, 2013, 41(2), 118-130.
[http://dx.doi.org/10.1159/000351153] [PMID: 23860588]
[12]
Hardiman, O.; Al-Chalabi, A.; Brayne, C.; Beghi, E.; van den Berg, L.H.; Chio, A.; Martin, S.; Logroscino, G.; Rooney, J. The changing picture of amyotrophic lateral sclerosis: Lessons from European registers. J. Neurol. Neurosurg. Psychiatry, 2017, 88(7), 557-563.
[http://dx.doi.org/10.1136/jnnp-2016-314495] [PMID: 28285264]
[13]
Brooks, B.R.; Miller, R.G.; Swash, M.; Munsat, T.L. El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 2000, 1(5), 293-299.
[http://dx.doi.org/10.1080/146608200300079536] [PMID: 11464847]
[14]
van den Berg, L.H.; Sorenson, E.; Gronseth, G.; Macklin, E.A.; Andrews, J.; Baloh, R.H.; Benatar, M.; Berry, J.D.; Chio, A.; Corcia, P.; Genge, A.; Gubitz, A.K.; Lomen-Hoerth, C.; McDermott, C.J.; Pioro, E.P.; Rosenfeld, J.; Silani, V.; Turner, M.R.; Weber, M.; Brooks, B.R.; Miller, R.G.; Mitsumoto, H. Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials. Neurology, 2019, 92(14), e1610-e1623.
[http://dx.doi.org/10.1212/WNL.0000000000007242] [PMID: 30850440]
[15]
Shefner, J.M.; Al-Chalabi, A.; Baker, M.R.; Cui, L.Y.; de Carvalho, M.; Eisen, A.; Grosskreutz, J.; Hardiman, O.; Henderson, R.; Matamala, J.M.; Mitsumoto, H.; Paulus, W.; Simon, N.; Swash, M.; Talbot, K.; Turner, M.R.; Ugawa, Y.; van den Berg, L.H.; Verdugo, R.; Vucic, S.; Kaji, R.; Burke, D.; Kiernan, M.C. A proposal for new diagnostic criteria for ALS. Clin. Neurophysiol., 2020, 131(8), 1975-1978.
[http://dx.doi.org/10.1016/j.clinph.2020.04.005] [PMID: 32387049]
[16]
Bradley, W.G.; Andrew, A.S.; Traynor, B.J.; Chiò, A.; Butt, T.H.; Stommel, E.W. Gene-environment-time interactions in neurodegenerative diseases: Hypotheses and research approaches. Ann. Neurosci., 2018, 25(4), 261-267.
[http://dx.doi.org/10.1159/000495321] [PMID: 31000966]
[17]
Rossi, F.H. Pathophysiology of Amyotrophic Lateral Sclerosis; IntechOpen: Rijeka, 2013.
[http://dx.doi.org/10.5772/56562]
[18]
Schweingruber, C.; Hedlund, E. The cell autonomous and non-cell autonomous aspects of neuronal vulnerability and resilience in amyotrophic lateral sclerosis. Biology, 2022, 11(8), 1191.
[http://dx.doi.org/10.3390/biology11081191] [PMID: 36009818]
[19]
Turner, M.R.; Hardiman, O.; Benatar, M.; Brooks, B.R.; Chio, A.; de Carvalho, M.; Ince, P.G.; Lin, C.; Miller, R.G.; Mitsumoto, H.; Nicholson, G.; Ravits, J.; Shaw, P.J.; Swash, M.; Talbot, K.; Traynor, B.J.; Van den Berg, L.H.; Veldink, J.H.; Vucic, S.; Kiernan, M.C. Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol., 2013, 12(3), 310-322.
[http://dx.doi.org/10.1016/S1474-4422(13)70036-X] [PMID: 23415570]
[20]
Mejzini, R.; Flynn, L.L.; Pitout, I.L.; Fletcher, S.; Wilton, S.D.; Akkari, P.A. ALS genetics, mechanisms, and therapeutics: Where are we now? Front. Neurosci., 2019, 13, 1310.
[http://dx.doi.org/10.3389/fnins.2019.01310] [PMID: 31866818]
[21]
Ryan, M.; Heverin, M.; McLaughlin, R.L.; Hardiman, O. Lifetime risk and heritability of amyotrophic lateral sclerosis. JAMA Neurol., 2019, 76(11), 1367-1374.
[http://dx.doi.org/10.1001/jamaneurol.2019.2044] [PMID: 31329211]
[22]
Fifita, J.A.; Williams, K.L.; Sundaramoorthy, V.; Mccann, E.P.; Nicholson, G.A.; Atkin, J.D.; Blair, I.P. A novel amyotrophic lateral sclerosis mutation in OPTN induces ER stress and Golgi fragmentation in vitro. Amyotroph. Lateral Scler. Frontotemporal Degener., 2017, 18(1-2), 126-133.
[http://dx.doi.org/10.1080/21678421.2016.1218517] [PMID: 27534431]
[23]
Brown, C. Non-Familial ALS: A tangled web. Nature, 2017, 550(7676), S109-S111.
[http://dx.doi.org/10.1038/550S109a] [PMID: 29045373]
[24]
Cooper-Knock, J.; Harvey, C.; Zhang, S.; Moll, T.; Timpanaro, I.S.; Kenna, K.P.; Iacoangeli, A.; Veldink, J.H. Advances in the genetic classification of amyotrophic lateral sclerosis. Curr. Opin. Neurol., 2021, 34(5), 756-764.
[http://dx.doi.org/10.1097/WCO.0000000000000986] [PMID: 34343141]
[25]
van Rheenen, W.; van der Spek, R.A.A.; Bakker, M.K.; van Vugt, J.J.F.A.; Hop, P.J.; Zwamborn, R.A.J.; de Klein, N.; Westra, H.J.; Bakker, O.B.; Deelen, P.; Shireby, G.; Hannon, E.; Moisse, M.; Baird, D.; Restuadi, R.; Dolzhenko, E.; Dekker, A.M.; Gawor, K.; Westeneng, H.J.; Tazelaar, G.H.P.; van Eijk, K.R.; Kooyman, M.; Byrne, R.P.; Doherty, M.; Heverin, M.; Al Khleifat, A.; Iacoangeli, A.; Shatunov, A.; Ticozzi, N.; Cooper-Knock, J.; Smith, B.N.; Gromicho, M.; Chandran, S.; Pal, S.; Morrison, K.E.; Shaw, P.J.; Hardy, J.; Orrell, R.W.; Sendtner, M.; Meyer, T.; Başak, N.; van der Kooi, A.J.; Ratti, A.; Fogh, I.; Gellera, C.; Lauria, G.; Corti, S.; Cereda, C.; Sproviero, D.; D’Alfonso, S.; Sorarù, G.; Siciliano, G.; Filosto, M.; Padovani, A.; Chiò, A.; Calvo, A.; Moglia, C.; Brunetti, M.; Canosa, A.; Grassano, M.; Beghi, E.; Pupillo, E.; Logroscino, G.; Nefussy, B.; Osmanovic, A.; Nordin, A.; Lerner, Y.; Zabari, M.; Gotkine, M.; Baloh, R.H.; Bell, S.; Vourc’h, P.; Corcia, P.; Couratier, P.; Millecamps, S.; Meininger, V.; Salachas, F.; Mora Pardina, J.S.; Assialioui, A.; Rojas-García, R.; Dion, P.A.; Ross, J.P.; Ludolph, A.C.; Weishaupt, J.H.; Brenner, D.; Freischmidt, A.; Bensimon, G.; Brice, A.; Durr, A.; Payan, C.A.M.; Saker-Delye, S.; Wood, N.W.; Topp, S.; Rademakers, R.; Tittmann, L.; Lieb, W.; Franke, A.; Ripke, S.; Braun, A.; Kraft, J.; Whiteman, D.C.; Olsen, C.M.; Uitterlinden, A.G.; Hofman, A.; Rietschel, M.; Cichon, S.; Nöthen, M.M.; Amouyel, P.; Comi, G.; Riva, N.; Lunetta, C.; Gerardi, F.; Cotelli, M.S.; Rinaldi, F.; Chiveri, L.; Guaita, M.C.; Perrone, P.; Ceroni, M.; Diamanti, L.; Ferrarese, C.; Tremolizzo, L.; Delodovici, M.L.; Bono, G.; Canosa, A.; Manera, U.; Vasta, R.; Bombaci, A.; Casale, F.; Fuda, G.; Salamone, P.; Iazzolino, B.; Peotta, L.; Cugnasco, P.; De Marco, G.; Torrieri, M.C.; Palumbo, F.; Gallone, S.; Barberis, M.; Sbaiz, L.; Gentile, S.; Mauro, A.; Mazzini, L.; De Marchi, F.; Corrado, L.; D’Alfonso, S.; Bertolotto, A.; Gionco, M.; Leotta, D.; Odddenino, E.; Imperiale, D.; Cavallo, R.; Pignatta, P.; De Mattei, M.; Geda, C.; Papurello, D.M.; Gusmaroli, G.; Comi, C.; Labate, C.; Ruiz, L.; Ferrandi, D.; Rota, E.; Aguggia, M.; Di Vito, N.; Meineri, P.; Ghiglione, P.; Launaro, N.; Dotta, M.; Di Sapio, A.; Giardini, G.; Tiloca, C.; Peverelli, S.; Taroni, F.; Pensato, V.; Castellotti, B.; Comi, G.P.; Del Bo, R.; Ceroni, M.; Gagliardi, S.; Corrado, L.; Mazzini, L.; Raggi, F.; Simoncini, C.; Lo Gerfo, A.; Inghilleri, M.; Ferlini, A.; Simone, I.L.; Passarella, B.; Guerra, V.; Zoccolella, S.; Nozzoli, C.; Mundi, C.; Leone, M.; Zarrelli, M.; Tamma, F.; Valluzzi, F.; Calabrese, G.; Boero, G.; Rini, A.; Traynor, B.J.; Singleton, A.B.; Mitne Neto, M.; Cauchi, R.J.; Ophoff, R.A.; Wiedau-Pazos, M.; Lomen-Hoerth, C.; van Deerlin, V.M.; Grosskreutz, J.; Roediger, A.; Gaur, N.; Jörk, A.; Barthel, T.; Theele, E.; Ilse, B.; Stubendorff, B.; Witte, O.W.; Steinbach, R.; Hübner, C.A.; Graff, C.; Brylev, L.; Fominykh, V.; Demeshonok, V.; Ataulina, A.; Rogelj, B.; Koritnik, B.; Zidar, J.; Ravnik-Glavač, M.; Glavač, D.; Stević, Z.; Drory, V.; Povedano, M.; Blair, I.P.; Kiernan, M.C.; Benyamin, B.; Henderson, R.D.; Furlong, S.; Mathers, S.; McCombe, P.A.; Needham, M.; Ngo, S.T.; Nicholson, G.A.; Pamphlett, R.; Rowe, D.B.; Steyn, F.J.; Williams, K.L.; Mather, K.A.; Sachdev, P.S.; Henders, A.K.; Wallace, L.; de Carvalho, M.; Pinto, S.; Petri, S.; Weber, M.; Rouleau, G.A.; Silani, V.; Curtis, C.J.; Breen, G.; Glass, J.D.; Brown, R.H., Jr; Landers, J.E.; Shaw, C.E.; Andersen, P.M.; Groen, E.J.N.; van Es, M.A.; Pasterkamp, R.J.; Fan, D.; Garton, F.C.; McRae, A.F.; Davey Smith, G.; Gaunt, T.R.; Eberle, M.A.; Mill, J.; McLaughlin, R.L.; Hardiman, O.; Kenna, K.P.; Wray, N.R.; Tsai, E.; Runz, H.; Franke, L.; Al-Chalabi, A.; Van Damme, P.; van den Berg, L.H.; Veldink, J.H. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology. Nat. Genet., 2021, 53(12), 1636-1648.
[http://dx.doi.org/10.1038/s41588-021-00973-1] [PMID: 34873335]
[26]
Casas, C.; Manzano, R.; Vaz, R.; Osta, R.; Brites, D. Synaptic failure: Focus in an integrative view of ALS. Brain Plast., 2016, 1(2), 159-175.
[http://dx.doi.org/10.3233/BPL-140001] [PMID: 29765840]
[27]
Fogarty, M. Amyotrophic lateral sclerosis as a synaptopathy. Neural Regen. Res., 2019, 14(2), 189-192.
[http://dx.doi.org/10.4103/1673-5374.244782] [PMID: 30530995]
[28]
Genç, B.; Jara, J.H.; Lagrimas, A.K.B.; Pytel, P.; Roos, R.P.; Mesulam, M.M.; Geula, C.; Bigio, E.H.; Özdinler, P.H. Apical dendrite degeneration, a novel cellular pathology for Betz cells in ALS. Sci. Rep., 2017, 7(1), 41765.
[http://dx.doi.org/10.1038/srep41765] [PMID: 28165465]
[29]
Guidotti, G.; Scarlata, C.; Brambilla, L.; Rossi, D. Tumor necrosis factor alpha in amyotrophic lateral sclerosis: Friend or foe? Cells, 2021, 10(3), 518.
[http://dx.doi.org/10.3390/cells10030518] [PMID: 33804386]
[30]
Bursch, F.; Kalmbach, N.; Naujock, M.; Staege, S.; Eggenschwiler, R.; Abo-Rady, M.; Japtok, J.; Guo, W.; Hensel, N.; Reinhardt, P.; Boeckers, T.M.; Cantz, T.; Sterneckert, J.; Van Den Bosch, L.; Hermann, A.; Petri, S.; Wegner, F. Altered calcium dynamics and glutamate receptor properties in iPSC-derived motor neurons from ALS patients with C9orf72, FUS, SOD1 or TDP43 mutations. Hum. Mol. Genet., 2019, 28(17), 2835-2850.
[http://dx.doi.org/10.1093/hmg/ddz107] [PMID: 31108504]
[31]
Bonifacino, T.; Provenzano, F.; Gallia, E.; Ravera, S.; Torazza, C.; Bossi, S.; Ferrando, S.; Puliti, A.; Van Den Bosch, L.; Bonanno, G.; Milanese, M. In-vivo genetic ablation of metabotropic glutamate receptor type 5 slows down disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis., 2019, 129, 79-92.
[http://dx.doi.org/10.1016/j.nbd.2019.05.007] [PMID: 31102766]
[32]
Vermeiren, Y.; Janssens, J.; Van Dam, D.; De Deyn, P.P. Serotonergic dysfunction in amyotrophic lateral sclerosis and parkinson’s disease: Similar mechanisms, dissimilar outcomes. Front. Neurosci., 2018, 12, 185.
[http://dx.doi.org/10.3389/fnins.2018.00185] [PMID: 29615862]
[33]
Yang, Y.; Gozen, O.; Watkins, A.; Lorenzini, I.; Lepore, A.; Gao, Y.; Vidensky, S.; Brennan, J.; Poulsen, D.; Won Park, J.; Li Jeon, N.; Robinson, M.B.; Rothstein, J.D. Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron, 2009, 61(6), 880-894.
[http://dx.doi.org/10.1016/j.neuron.2009.02.010] [PMID: 19323997]
[34]
Scamps, F.; Aimond, F.; Hilaire, C.; Raoul, C. Synaptic transmission and motoneuron excitability defects in amyotrophic lateral sclerosis. In: Amyotrophic Lateral Sclerosis; Exon Publications: Brisbane (AU), 2021.
[http://dx.doi.org/10.36255/exonpublications.amyotrophiclateralsclerosis.synaptictransmission.2021]
[35]
Sunico, C.R.; Domínguez, G.; García-Verdugo, J.M.; Osta, R.; Montero, F.; Moreno-López, B. Reduction in the motoneuron inhibitory/excitatory synaptic ratio in an early-symptomatic mouse model of amyotrophic lateral sclerosis. Brain Pathol., 2011, 21(1), 1-15.
[http://dx.doi.org/10.1111/j.1750-3639.2010.00417.x] [PMID: 20653686]
[36]
Sirabella, R.; Valsecchi, V.; Anzilotti, S.; Cuomo, O.; Vinciguerra, A.; Cepparulo, P.; Brancaccio, P.; Guida, N.; Blondeau, N.; Canzoniero, L.M.T.; Franco, C.; Amoroso, S.; Annunziato, L.; Pignataro, G. Ionic homeostasis maintenance in ALS: Focus on new therapeutic targets. Front. Neurosci., 2018, 12, 510.
[http://dx.doi.org/10.3389/fnins.2018.00510] [PMID: 30131665]
[37]
Ragagnin, A.M.G.; Shadfar, S.; Vidal, M.; Jamali, M.S.; Atkin, J.D. Motor neuron susceptibility in ALS/FTD. Front. Neurosci., 2019, 13, 532.
[http://dx.doi.org/10.3389/fnins.2019.00532] [PMID: 31316328]
[38]
Tateno, M.; Kato, S.; Sakurai, T.; Nukina, N.; Takahashi, R.; Araki, T. Mutant SOD1 impairs axonal transport of choline acetyltransferase and acetylcholine release by sequestering KAP3. Hum. Mol. Genet., 2009, 18(5), 942-955.
[http://dx.doi.org/10.1093/hmg/ddn422] [PMID: 19088126]
[39]
Verma, S.; Khurana, S.; Vats, A.; Sahu, B.; Ganguly, N.K.; Chakraborti, P.; Gourie-Devi, M.; Taneja, V. Neuromuscular junction dysfunction in amyotrophic lateral sclerosis. Mol. Neurobiol., 2022, 59(3), 1502-1527.
[http://dx.doi.org/10.1007/s12035-021-02658-6] [PMID: 34997540]
[40]
Lin, C.Y.; Wu, C.L.; Lee, K.Z.; Chen, Y.J.; Zhang, P.H.; Chang, C.Y.; Harn, H.J.; Lin, S.Z.; Tsai, H.J. Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA. eLife, 2019, 8, e49175.
[http://dx.doi.org/10.7554/eLife.49175] [PMID: 31361595]
[41]
Venkova, K.; Christov, A.; Kamaluddin, Z.; Kobalka, P.; Siddiqui, S.; Hensley, K. Semaphorin 3A signaling through neuropilin-1 is an early trigger for distal axonopathy in the SOD1G93A mouse model of amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol., 2014, 73(7), 702-713.
[http://dx.doi.org/10.1097/NEN.0000000000000086] [PMID: 24918638]
[42]
Moloney, E.B.; de Winter, F.; Verhaagen, J. ALS as a distal axonopathy: Molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease. Front. Neurosci., 2014, 8, 252.
[http://dx.doi.org/10.3389/fnins.2014.00252] [PMID: 25177267]
[43]
Krieger, C.; Wang, S.J.H.; Yoo, S.H.; Harden, N. Adducin at the neuromuscular junction in amyotrophic lateral sclerosis: Hanging on for dear life. Front. Cell. Neurosci., 2016, 10, 11.
[http://dx.doi.org/10.3389/fncel.2016.00011] [PMID: 26858605]
[44]
Palma, E.; Reyes-Ruiz, J.M.; Lopergolo, D.; Roseti, C.; Bertollini, C.; Ruffolo, G.; Cifelli, P.; Onesti, E.; Limatola, C.; Miledi, R.; Inghilleri, M. Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy. Proc. Natl. Acad. Sci. USA, 2016, 113(11), 3060-3065.
[http://dx.doi.org/10.1073/pnas.1600251113] [PMID: 26929355]
[45]
Van Hoecke, A.; Schoonaert, L.; Lemmens, R.; Timmers, M.; Staats, K.A.; Laird, A.S.; Peeters, E.; Philips, T.; Goris, A.; Dubois, B.; Andersen, P.M.; Al-Chalabi, A.; Thijs, V.; Turnley, A.M.; van Vught, P.W.; Veldink, J.H.; Hardiman, O.; Van Den Bosch, L.; Gonzalez-Perez, P.; Van Damme, P.; Brown, R.H., Jr; van den Berg, L.H.; Robberecht, W. EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nat. Med., 2012, 18(9), 1418-1422.
[http://dx.doi.org/10.1038/nm.2901] [PMID: 22922411]
[46]
Murray, L.M.; Talbot, K.; Gillingwater, T.H. Review: Neuromuscular synaptic vulnerability in motor neurone disease: amyotrophic lateral sclerosis and spinal muscular atrophy. Neuropathol. Appl. Neurobiol., 2010, 36(2), 133-156.
[http://dx.doi.org/10.1111/j.1365-2990.2010.01061.x] [PMID: 20202121]
[47]
Schomburg, E.D.; Steffens, H.; Zschüntzsch, J.; Dibaj, P.; Keller, B.U. Fatigability of spinal reflex transmission in a mouse model (SOD1G93A ) of amyotrophic lateral sclerosis. Muscle Nerve, 2011, 43(2), 230-236.
[http://dx.doi.org/10.1002/mus.21835] [PMID: 21254088]
[48]
Rocha, M.C.; Pousinha, P.A.; Correia, A.M.; Sebastião, A.M.; Ribeiro, J.A. Early changes of neuromuscular transmission in the (SOD1G93A ) mice model of ALS start long before motor symptoms onset. PLoS One, 2013, 8(9), e73846.
[http://dx.doi.org/10.1371/journal.pone.0073846] [PMID: 24040091]
[49]
Carrasco, D.I.; Seburn, K.L.; Pinter, M.J. Altered terminal Schwann cell morphology precedes denervation in SOD1 mice. Exp. Neurol., 2016, 275(0 1), 172-181.
[http://dx.doi.org/10.1016/j.expneurol.2015.09.014] [PMID: 26416261]
[50]
Manzano, R.; Toivonen, J.M.; Calvo, A.C.; Oliván, S.; Zaragoza, P.; Rodellar, C.; Montarras, D.; Osta, R. Altered in vitro proliferation of mouse SOD1-G93A skeletal muscle satellite cells. Neurodegener. Dis., 2013, 11(3), 153-164.
[http://dx.doi.org/10.1159/000338061] [PMID: 22797053]
[51]
Nijssen, J.; Comley, L.H.; Hedlund, E. Motor neuron vulnerability and resistance in amyotrophic lateral sclerosis. Acta Neuropathol., 2017, 133(6), 863-885.
[http://dx.doi.org/10.1007/s00401-017-1708-8] [PMID: 28409282]
[52]
Rochat, C.; Schneider, B.L.; Bernard-Marissal, N. Selective vulnerability of neuronal subtypes in ALS: A fertile ground for the identification of therapeutic targets. In: Update on Amyotrophic Lateral Sclerosis; InTech, 2016.
[http://dx.doi.org/10.5772/63703]
[53]
Ruegsegger, C.; Maharjan, N.; Goswami, A.; Filézac de L’Etang, A.; Weis, J.; Troost, D.; Heller, M.; Gut, H.; Saxena, S. Aberrant association of misfolded SOD1 with Na+/K+ATPase-α3 impairs its activity and contributes to motor neuron vulnerability in ALS. Acta Neuropathol., 2016, 131(3), 427-451.
[http://dx.doi.org/10.1007/s00401-015-1510-4] [PMID: 26619836]
[54]
Ramírez-Jarquín, U.N.; Tapia, R. Excitatory and inhibitory neuronal circuits in the spinal cord and their role in the control of motor neuron function and degeneration. ACS Chem. Neurosci., 2018, 9(2), 211-216.
[http://dx.doi.org/10.1021/acschemneuro.7b00503] [PMID: 29350907]
[55]
Orr, B.O.; Hauswirth, A.G.; Celona, B.; Fetter, R.D.; Zunino, G.; Kvon, E.Z.; Zhu, Y.; Pennacchio, L.A.; Black, B.L.; Davis, G.W. Presynaptic homeostasis opposes disease progression in mouse models of ALS-Like degeneration: Evidence for homeostatic neuroprotection. Neuron, 2020, 107(1), 95-111.e6.
[http://dx.doi.org/10.1016/j.neuron.2020.04.009] [PMID: 32380032]
[56]
Wijesekera, L.C.; Nigel Leigh, P. Amyotrophic lateral sclerosis. Orphanet J. Rare Dis., 2009, 4(1), 3.
[http://dx.doi.org/10.1186/1750-1172-4-3] [PMID: 19192301]
[57]
Isaacs, J.D.; Dean, A.F.; Shaw, C.E.; Al-Chalabi, A.; Mills, K.R.; Leigh, P.N. Amyotrophic lateral sclerosis with sensory neuropathy: Part of a multisystem disorder? J. Neurol. Neurosurg. Psychiatry, 2006, 78(7), 750-753.
[http://dx.doi.org/10.1136/jnnp.2006.098798] [PMID: 17575021]
[58]
Seki, S.; Yamamoto, T.; Quinn, K.; Spigelman, I.; Pantazis, A.; Olcese, R.; Wiedau-Pazos, M.; Chandler, S.H.; Venugopal, S. Circuit-specific early impairment of proprioceptive sensory neurons in the SOD1G93A mouse model for ALS. J. Neurosci., 2019, 39(44), 8798-8815.
[http://dx.doi.org/10.1523/JNEUROSCI.1214-19.2019] [PMID: 31530644]
[59]
Vaughan, S.K.; Sutherland, N.M.; Zhang, S.; Hatzipetros, T.; Vieira, F.; Valdez, G. The ALS-inducing factors, TDP43A315T and SOD1G93A , directly affect and sensitize sensory neurons to stress. Sci. Rep., 2018, 8(1), 16582.
[http://dx.doi.org/10.1038/s41598-018-34510-8] [PMID: 30410094]
[60]
Lalancette-Hebert, M.; Sharma, A.; Lyashchenko, A.K.; Shneider, N.A. Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS. Proc. Natl. Acad. Sci. USA, 2016, 113(51), E8316-E8325.
[http://dx.doi.org/10.1073/pnas.1605210113] [PMID: 27930290]
[61]
Brownstone, R.M.; Lancelin, C. Escape from homeostasis: spinal microcircuits and progression of amyotrophic lateral sclerosis. J. Neurophysiol., 2018, 119(5), 1782-1794.
[http://dx.doi.org/10.1152/jn.00331.2017] [PMID: 29384454]
[62]
Ashford, B.A.; Boche, D.; Cooper-Knock, J.; Heath, P.R.; Simpson, J.E.; Highley, J.R. Review: Microglia in motor neuron disease. Neuropathol. Appl. Neurobiol., 2021, 47(2), 179-197.
[http://dx.doi.org/10.1111/nan.12640] [PMID: 32594542]
[63]
Gomes, C.; Sequeira, C.; Barbosa, M.; Cunha, C.; Vaz, A.R.; Brites, D. Astrocyte regional diversity in ALS includes distinct aberrant phenotypes with common and causal pathological processes. Exp. Cell Res., 2020, 395(2), 112209.
[http://dx.doi.org/10.1016/j.yexcr.2020.112209] [PMID: 32739211]
[64]
Geloso, M.C.; Corvino, V.; Marchese, E.; Serrano, A.; Michetti, F.; D’Ambrosi, N. The dual role of microglia in ALS: Mechanisms and therapeutic approaches. Front. Aging Neurosci., 2017, 9, 242.
[http://dx.doi.org/10.3389/fnagi.2017.00242] [PMID: 28790913]
[65]
Trolese, M.C.; Mariani, A.; Terao, M.; de Paola, M.; Fabbrizio, P.; Sironi, F.; Kurosaki, M.; Bonanno, S.; Marcuzzo, S.; Bernasconi, P.; Trojsi, F.; Aronica, E.; Bendotti, C.; Nardo, G. CXCL13/] CXCR5 signalling is pivotal to preserve motor neurons in amyotrophic lateral sclerosis. EBioMedicine, 2020, 62, 103097.
[http://dx.doi.org/10.1016/j.ebiom.2020.103097] [PMID: 33161233]
[66]
Hensley, K.; Mhatre, M.; Mou, S.; Pye, Q.N.; Stewart, C.; West, M.; Williamson, K.S. On the relation of oxidative stress to neuroinflammation: Lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Antioxid. Redox Signal., 2006, 8(11-12), 2075-2087.
[http://dx.doi.org/10.1089/ars.2006.8.2075] [PMID: 17034351]
[67]
Puentes, F.; Malaspina, A.; van Noort, J.M.; Amor, S. Non-neuronal cells in ALS: Role of glial, immune cells and blood-CNS barriers. Brain Pathol., 2016, 26(2), 248-257.
[http://dx.doi.org/10.1111/bpa.12352] [PMID: 26780491]
[68]
Santoni, G.; Cardinali, C.; Morelli, M.; Santoni, M.; Nabissi, M.; Amantini, C. Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J. Neuroinflammation, 2015, 12(1), 21.
[http://dx.doi.org/10.1186/s12974-015-0239-2] [PMID: 25644504]
[69]
Ouali, A.N.; Schurr, C.; Olde Heuvel, F.; Tang, L.; Li, Q.; Tasdogan, A.; Kimbara, A.; Nettekoven, M.; Ottaviani, G.; Raposo, C.; Röver, S.; Rogers-Evans, M.; Rothenhäusler, B.; Ullmer, C.; Fingerle, J.; Grether, U.; Knuesel, I.; Boeckers, T.M.; Ludolph, A.; Wirth, T.; Roselli, F.; Baumann, B. NF‐κB activation in astrocytes drives a stage‐specific beneficial neuroimmunological response in ALS. EMBO J., 2018, 37(16), e98697.
[http://dx.doi.org/10.15252/embj.201798697] [PMID: 29875132]
[70]
Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Münch, A.E.; Chung, W.S.; Peterson, T.C.; Wilton, D.K.; Frouin, A.; Napier, B.A.; Panicker, N.; Kumar, M.; Buckwalter, M.S.; Rowitch, D.H.; Dawson, V.L.; Dawson, T.M.; Stevens, B.; Barres, B.A. Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 2017, 541(7638), 481-487.
[http://dx.doi.org/10.1038/nature21029] [PMID: 28099414]
[71]
Vaz, S.H.; Pinto, S.; Sebastião, A.M.; Brites, D. Astrocytes in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler; Araki, T., Ed.; Exon Publications: Brisbane, 2021.
[http://dx.doi.org/10.36255/exonpublications.amyotrophiclateralsclerosis.astrocytes.2021]
[72]
Zhao, W.; Beers, D.R.; Appel, S.H. Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J. Neuroimmune Pharmacol., 2013, 8(4), 888-899.
[http://dx.doi.org/10.1007/s11481-013-9489-x] [PMID: 23881705]
[73]
Johann, S.; Heitzer, M.; Kanagaratnam, M.; Goswami, A.; Rizo, T.; Weis, J.; Troost, D.; Beyer, C. NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients. Glia, 2015, 63(12), 2260-2273.
[http://dx.doi.org/10.1002/glia.22891] [PMID: 26200799]
[74]
MacLean, M.; Juranek, J.; Cuddapah, S.; López-Díez, R.; Ruiz, H.H.; Hu, J.; Frye, L.; Li, H.; Gugger, P.F.; Schmidt, A.M. Microglia RAGE exacerbates the progression of neurodegeneration within the SOD1G93A murine model of amyotrophic lateral sclerosis in a sex-dependent manner. J. Neuroinflammation, 2021, 18(1), 139.
[http://dx.doi.org/10.1186/s12974-021-02191-2] [PMID: 34130712]
[75]
Eitan, C.; Siany, A.; Barkan, E.; Olender, T.; van Eijk, K.R.; Moisse, M.; Farhan, S.M.K.; Danino, Y.M.; Yanowski, E.; Marmor-Kollet, H.; Rivkin, N.; Yacovzada, N.S.; Hung, S.T.; Cooper-Knock, J.; Yu, C.H.; Louis, C.; Masters, S.L.; Kenna, K.P.; van der Spek, R.A.A.; Sproviero, W.; Al Khleifat, A.; Iacoangeli, A.; Shatunov, A.; Jones, A.R.; Elbaz-Alon, Y.; Cohen, Y.; Chapnik, E.; Rothschild, D.; Weissbrod, O.; Beck, G.; Ainbinder, E.; Ben-Dor, S.; Werneburg, S.; Schafer, D.P.; Brown, R.H., Jr; Shaw, P.J.; Van Damme, P.; van den Berg, L.H.; Phatnani, H.; Segal, E.; Ichida, J.K.; Al-Chalabi, A.; Veldink, J.H.; Cooper-Knock, J.; Kenna, K.P.; Van Damme, P.; van den Berg, L.H.; Hornstein, E.; Hornstein, E. Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3′UTR protect against ALS. Nat. Neurosci., 2022, 25(4), 433-445.
[http://dx.doi.org/10.1038/s41593-022-01040-6] [PMID: 35361972]
[76]
Beers, D.R.; Henkel, J.S.; Zhao, W.; Wang, J.; Appel, S.H. CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc. Natl. Acad. Sci. USA, 2008, 105(40), 15558-15563.
[http://dx.doi.org/10.1073/pnas.0807419105] [PMID: 18809917]
[77]
Henkel, J.S.; Beers, D.R.; Wen, S.; Rivera, A.L.; Toennis, K.M.; Appel, J.E.; Zhao, W.; Moore, D.H.; Powell, S.Z.; Appel, S.H. Regulatory T‐lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol. Med., 2013, 5(1), 64-79.
[http://dx.doi.org/10.1002/emmm.201201544] [PMID: 23143995]
[78]
McCombe, P.A.; Lee, J.D.; Woodruff, T.M.; Henderson, R.D. The peripheral immune system and amyotrophic lateral sclerosis. Front. Neurol., 2020, 11, 279.
[http://dx.doi.org/10.3389/fneur.2020.00279] [PMID: 32373052]
[79]
Volonté, C.; Apolloni, S.; Parisi, C.; Amadio, S. Purinergic contribution to amyotrophic lateral sclerosis. Neuropharmacology, 2016, 104, 180-193.
[http://dx.doi.org/10.1016/j.neuropharm.2015.10.026] [PMID: 26514402]
[80]
Sta, M.; Sylva-Steenland, R.M.R.; Casula, M.; de Jong, J.M.B.V.; Troost, D.; Aronica, E.; Baas, F. Innate and adaptive immunity in amyotrophic lateral sclerosis: Evidence of complement activation. Neurobiol. Dis., 2011, 42(3), 211-220.
[http://dx.doi.org/10.1016/j.nbd.2011.01.002] [PMID: 21220013]
[81]
Kakaroubas, N.; Brennan, S.; Keon, M.; Saksena, N.K. Pathomechanisms of blood-brain barrier disruption in ALS. Neurosci. J., 2019, 2019, 1-16.
[http://dx.doi.org/10.1155/2019/2537698] [PMID: 31380411]
[82]
Saul, J.; Hutchins, E.; Reiman, R.; Saul, M.; Ostrow, L.W.; Harris, B.T.; Van Keuren-Jensen, K.; Bowser, R.; Bakkar, N. Global alterations to the choroid plexus blood-CSF barrier in amyotrophic lateral sclerosis. Acta Neuropathol. Commun., 2020, 8(1), 92.
[http://dx.doi.org/10.1186/s40478-020-00968-9] [PMID: 32586411]
[83]
Bowerman, M. The neuroinflammation in the physiopathology of amyotrophic lateral sclerosis. In: Curr. Adv. Amyotrophic Lateral Sclerosis; InTech, 2013.
[http://dx.doi.org/10.5772/56489]
[84]
Jiang, L.L.; Zhu, B.; Zhao, Y.; Li, X.; Liu, T.; Pina-Crespo, J.; Zhou, L.; Xu, W.; Rodriguez, M.J.; Yu, H.; Cleveland, D.W.; Ravits, J.; Da Cruz, S.; Long, T.; Zhang, D.; Huang, T.Y.; Xu, H. Membralin deficiency dysregulates astrocytic glutamate homeostasis, leading to ALS-like impairment. J. Clin. Invest., 2019, 129(8), 3103-3120.
[http://dx.doi.org/10.1172/JCI127695] [PMID: 31112137]
[85]
Yin, X.; Wang, S.; Qi, Y.; Wang, X.; Jiang, H.; Wang, T.; Yang, Y.; Wang, Y.; Zhang, C.; Feng, H. Astrocyte elevated gene-1 is a novel regulator of astrogliosis and excitatory amino acid transporter-2 via interplaying with nuclear factor-κB signaling in astrocytes from amyotrophic lateral sclerosis mouse model with hSOD1 G93A mutation. Mol. Cell. Neurosci., 2018, 90, 1-11.
[http://dx.doi.org/10.1016/j.mcn.2018.05.004] [PMID: 29777762]
[86]
Rosenblum, L.T.; Shamamandri-Markandaiah, S.; Ghosh, B.; Foran, E.; Lepore, A.C.; Pasinelli, P.; Trotti, D. Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS. Exp. Neurol., 2017, 292, 145-153.
[http://dx.doi.org/10.1016/j.expneurol.2017.03.014] [PMID: 28342750]
[87]
Chen, L.C.; Smith, A.P.; Ben, Y.; Zukic, B.; Ignacio, S.; Moore, D.; Lee, N.M. Temporal gene expression patterns in G93A/SOD1 mouse. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 2004, 5(3), 164-171.
[http://dx.doi.org/10.1080/14660820410017091] [PMID: 15512905]
[88]
Lopez-Lopez, A.; Gamez, J.; Syriani, E.; Morales, M.; Salvado, M.; Rodríguez, M.J.; Mahy, N.; Vidal-Taboada, J.M. CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis. PLoS One, 2014, 9(5), e96528.
[http://dx.doi.org/10.1371/journal.pone.0096528] [PMID: 24806473]
[89]
Tripathi, P.; Rodriguez-Muela, N.; Klim, J.R.; de Boer, A.S.; Agrawal, S.; Sandoe, J.; Lopes, C.S.; Ogliari, K.S.; Williams, L.A.; Shear, M.; Rubin, L.L.; Eggan, K.; Zhou, Q. Reactive astrocytes promote ALS-like degeneration and intracellular protein aggregation in human motor neurons by disrupting autophagy through TGF-β1. Stem Cell Reports, 2017, 9(2), 667-680.
[http://dx.doi.org/10.1016/j.stemcr.2017.06.008] [PMID: 28712846]
[90]
Cassina, P.; Miquel, E.; Martínez-Palma, L.; Cassina, A. Glial metabolic reprogramming in amyotrophic lateral sclerosis. Neuroimmunomodulation, 2021, 28(4), 204-212.
[http://dx.doi.org/10.1159/000516926] [PMID: 34175843]
[91]
Moisse, K.; Strong, M.J. Innate immunity in amyotrophic lateral sclerosis. Biochim. Biophys. Acta Mol. Basis Dis., 2006, 1762(11-12), 1083-1093.
[http://dx.doi.org/10.1016/j.bbadis.2006.03.001] [PMID: 16624536]
[92]
Raffaele, S.; Boccazzi, M.; Fumagalli, M. Oligodendrocyte dysfunction in amyotrophic lateral sclerosis: Mechanisms and therapeutic perspectives. Cells, 2021, 10(3), 565.
[http://dx.doi.org/10.3390/cells10030565] [PMID: 33807572]
[93]
Ito, Y.; Ofengeim, D.; Najafov, A.; Das, S.; Saberi, S.; Li, Y.; Hitomi, J.; Zhu, H.; Chen, H.; Mayo, L.; Geng, J.; Amin, P.; DeWitt, J.P.; Mookhtiar, A.K.; Florez, M.; Ouchida, A.T.; Fan, J.; Pasparakis, M.; Kelliher, M.A.; Ravits, J.; Yuan, J. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science, 2016, 353(6299), 603-608.
[http://dx.doi.org/10.1126/science.aaf6803] [PMID: 27493188]
[94]
Liu, J.F.; Zheng, O.X.; Xin, J.G.; Chen, H.H.; Xin, J.J. How are necroptosis, immune dysfunction, and motoneuron death connected in amyotrophic lateral sclerosis? Neuroimmunol. Neuroinflamm., 2017, 4(6), 109-116.
[http://dx.doi.org/10.20517/2347-8659.2017.12]
[95]
Endo, F.; Komine, O.; Yamanaka, K. Neuroinflammation in motor neuron disease. Clin. Exp. Neuroimmunol., 2016, 7(2), 126-138.
[http://dx.doi.org/10.1111/cen3.12309]
[96]
Trias, E.; King, P.H.; Si, Y.; Kwon, Y.; Varela, V.; Ibarburu, S.; Kovacs, M.; Moura, I.C.; Beckman, J.S.; Hermine, O.; Barbeito, L. Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. JCI Insight, 2018, 3(19), e123249.
[http://dx.doi.org/10.1172/jci.insight.123249] [PMID: 30282815]
[97]
Kang, S.H.; Li, Y.; Fukaya, M.; Lorenzini, I.; Cleveland, D.W.; Ostrow, L.W.; Rothstein, J.D.; Bergles, D.E. Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis. Nat. Neurosci., 2013, 16(5), 571-579.
[http://dx.doi.org/10.1038/nn.3357] [PMID: 23542689]
[98]
Filipi, T.; Hermanova, Z.; Tureckova, J.; Vanatko, O.; Anderova, M. Glial cells—the strategic targets in amyotrophic lateral sclerosis treatment. J. Clin. Med., 2020, 9(1), 261.
[http://dx.doi.org/10.3390/jcm9010261] [PMID: 31963681]
[99]
Mishra, P.S.; Boutej, H.; Soucy, G.; Bareil, C.; Kumar, S.; Picher-Martel, V.; Dupré, N.; Kriz, J.; Julien, J.P. Transmission of ALS pathogenesis by the cerebrospinal fluid. Acta Neuropathol. Commun., 2020, 8(1), 65.
[http://dx.doi.org/10.1186/s40478-020-00943-4] [PMID: 32381112]
[100]
Sumitha, R.; Manjunatha, V.M.; Sabitha, R.K.; Alladi, P.A.; Nalini, A.; Rao, L.T.; Chandrasekhar Sagar, B.K.; Steinbusch, H.W.M.; Kramer, B.W.; Sathyaprabha, T.N.; Raju, T.R. Cerebrospinal fluid from patients with sporadic amyotrophic lateral sclerosis induces degeneration of motor neurons derived from human embryonic stem cells. Mol. Neurobiol., 2019, 56(2), 1014-1034.
[http://dx.doi.org/10.1007/s12035-018-1149-y] [PMID: 29858777]
[101]
Mishra, P.S.; Vijayalakshmi, K.; Nalini, A.; Sathyaprabha, T.N.; Kramer, B.W.; Alladi, P.A.; Raju, T.R. Etiogenic factors present in the cerebrospinal fluid from amyotrophic lateral sclerosis patients induce predominantly pro-inflammatory responses in microglia. J. Neuroinflammation, 2017, 14(1), 251.
[http://dx.doi.org/10.1186/s12974-017-1028-x] [PMID: 29246232]
[102]
Clement, A.M.; Nguyen, M.D.; Roberts, E.A.; Garcia, M.L.; Boillée, S.; Rule, M.; McMahon, A.P.; Doucette, W.; Siwek, D.; Ferrante, R.J.; Brown, R.H., Jr; Julien, J.P.; Goldstein, L.S.B.; Cleveland, D.W. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science, 2003, 302(5642), 113-117.
[http://dx.doi.org/10.1126/science.1086071] [PMID: 14526083]
[103]
Lobsiger, C.S.; Boillee, S.; McAlonis-Downes, M.; Khan, A.M.; Feltri, M.L.; Yamanaka, K.; Cleveland, D.W. Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Proc. Natl. Acad. Sci. USA, 2009, 106(11), 4465-4470.
[http://dx.doi.org/10.1073/pnas.0813339106] [PMID: 19251638]
[104]
Boillée, S.; Yamanaka, K.; Lobsiger, C.S.; Copeland, N.G.; Jenkins, N.A.; Kassiotis, G.; Kollias, G.; Cleveland, D.W. Onset and progression in inherited ALS determined by motor neurons and microglia. Science, 2006, 312(5778), 1389-1392.
[http://dx.doi.org/10.1126/science.1123511] [PMID: 16741123]
[105]
Van Harten, A.C.M.; Phatnani, H.; Przedborski, S. Non-cell-autonomous pathogenic mechanisms in amyotrophic lateral sclerosis. Trends Neurosci., 2021, 44(8), 658-668.
[http://dx.doi.org/10.1016/j.tins.2021.04.008] [PMID: 34006386]
[106]
Damme, M.; Suntio, T.; Saftig, P.; Eskelinen, E.L. Autophagy in neuronal cells: general principles and physiological and pathological functions. Acta Neuropathol., 2015, 129(3), 337-362.
[http://dx.doi.org/10.1007/s00401-014-1361-4] [PMID: 25367385]
[107]
Sasaki, S. Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol., 2011, 70(5), 349-359.
[http://dx.doi.org/10.1097/NEN.0b013e3182160690] [PMID: 21487309]
[108]
Fernando, R.; Castro, J.P.; Flore, T.; Deubel, S.; Grune, T.; Ott, C. Age-related maintenance of the autophagy-lysosomal system is dependent on skeletal muscle type. Oxid. Med. Cell. Longev., 2020, 2020, 1-8.
[http://dx.doi.org/10.1155/2020/4908162] [PMID: 32774673]
[109]
Amin, A.; Perera, N.D.; Beart, P.M.; Turner, B.J.; Shabanpoor, F. Amyotrophic lateral sclerosis and autophagy: Dysfunction and therapeutic targeting. Cells, 2020, 9(11), 2413.
[http://dx.doi.org/10.3390/cells9112413] [PMID: 33158177]
[110]
Fujikake, N.; Shin, M.; Shimizu, S. Association between autophagy and neurodegenerative diseases. Front. Neurosci., 2018, 12, 255.
[http://dx.doi.org/10.3389/fnins.2018.00255] [PMID: 29872373]
[111]
Chen, A.I.; Xiong, L.J.; Tong, Y.U.; Mao, M. Neuroprotective effect of brain-derived neurotrophic factor mediated by autophagy through the PI3K/Akt/mTOR pathway. Mol. Med. Rep., 2013, 8(4), 1011-1016.
[http://dx.doi.org/10.3892/mmr.2013.1628] [PMID: 23942837]
[112]
Ugolino, J.; Ji, Y.J.; Conchina, K.; Chu, J.; Nirujogi, R.S.; Pandey, A.; Brady, N.R.; Hamacher-Brady, A.; Wang, J. Loss of C9orf72 enhances autophagic activity via deregulated mTOR and TFEB signaling. PLoS Genet., 2016, 12(11), e1006443-e1006443.
[http://dx.doi.org/10.1371/journal.pgen.1006443] [PMID: 27875531]
[113]
Budini, M.; Buratti, E.; Morselli, E.; Criollo, A. Autophagy and its impact on neurodegenerative diseases: New roles for TDP-43 and C9orf72. Front. Mol. Neurosci., 2017, 10, 170.
[http://dx.doi.org/10.3389/fnmol.2017.00170] [PMID: 28611593]
[114]
Chew, J.; Cook, C.; Gendron, T.F.; Jansen-West, K.; del Rosso, G.; Daughrity, L.M.; Castanedes-Casey, M.; Kurti, A.; Stankowski, J.N.; Disney, M.D.; Rothstein, J.D.; Dickson, D.W.; Fryer, J.D.; Zhang, Y.J.; Petrucelli, L. Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy. Mol. Neurodegener., 2019, 14(1), 9.
[http://dx.doi.org/10.1186/s13024-019-0310-z] [PMID: 30767771]
[115]
Nguyen, D.K.H.; Thombre, R.; Wang, J. Autophagy as a common pathway in amyotrophic lateral sclerosis. Neurosci. Lett., 2019, 697, 34-48.
[http://dx.doi.org/10.1016/j.neulet.2018.04.006] [PMID: 29626651]
[116]
Oakes, J.A.; Davies, M.C.; Collins, M.O. TBK1: a new player in ALS linking autophagy and neuroinflammation. Mol. Brain, 2017, 10(1), 5.
[http://dx.doi.org/10.1186/s13041-017-0287-x] [PMID: 28148298]
[117]
Tak, Y.J.; Park, J.H.; Rhim, H.; Kang, S. ALS-related mutant SOD1 aggregates interfere with mitophagy by sequestering the autophagy receptor optineurin. Int. J. Mol. Sci., 2020, 21(20), 7525.
[http://dx.doi.org/10.3390/ijms21207525] [PMID: 33065963]
[118]
Zhang, Y.J.; Jansen-West, K.; Xu, Y.F.; Gendron, T.F.; Bieniek, K.F.; Lin, W.L.; Sasaguri, H.; Caulfield, T.; Hubbard, J.; Daughrity, L.; Chew, J.; Belzil, V.V.; Prudencio, M.; Stankowski, J.N.; Castanedes-Casey, M.; Whitelaw, E.; Ash, P.E.A.; DeTure, M.; Rademakers, R.; Boylan, K.B.; Dickson, D.W.; Petrucelli, L. Aggregation-prone c9FTD/ALS poly(GA) RAN-translated proteins cause neurotoxicity by inducing ER stress. Acta Neuropathol., 2014, 128(4), 505-524.
[http://dx.doi.org/10.1007/s00401-014-1336-5] [PMID: 25173361]
[119]
Soo, K.Y.; Sultana, J.; King, A.E.; Atkinson, R.A.K.; Warraich, S.T.; Sundaramoorthy, V.; Blair, I.; Farg, M.A.; Atkin, J.D. ALS-associated mutant FUS inhibits macroautophagy which is restored by overexpression of Rab1. Cell Death Discov., 2015, 1(1), 15030.
[http://dx.doi.org/10.1038/cddiscovery.2015.30] [PMID: 27551461]
[120]
Purice, M.D.; Taylor, J.P. Linking hnRNP function to ALS and FTD pathology. Front. Neurosci., 2018, 12, 326.
[http://dx.doi.org/10.3389/fnins.2018.00326] [PMID: 29867335]
[121]
Renaud, L.; Picher-Martel, V.; Codron, P.; Julien, J.P. Key role of UBQLN2 in pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol. Commun., 2019, 7(1), 103.
[http://dx.doi.org/10.1186/s40478-019-0758-7] [PMID: 31319884]
[122]
Burk, K.; Pasterkamp, R.J. Disrupted neuronal trafficking in amyotrophic lateral sclerosis. Acta Neuropathol., 2019, 137(6), 859-877.
[http://dx.doi.org/10.1007/s00401-019-01964-7] [PMID: 30721407]
[123]
Theunissen, F.; West, P.K.; Brennan, S.; Petrović, B.; Hooshmand, K.; Akkari, P.A.; Keon, M.; Guennewig, B. New perspectives on cytoskeletal dysregulation and mitochondrial mislocalization in amyotrophic lateral sclerosis. Transl. Neurodegener., 2021, 10(1), 46.
[http://dx.doi.org/10.1186/s40035-021-00272-z] [PMID: 34789332]
[124]
Kieran, D.; Hafezparast, M.; Bohnert, S.; Dick, J.R.T.; Martin, J.; Schiavo, G.; Fisher, E.M.C.; Greensmith, L. A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J. Cell Biol., 2005, 169(4), 561-567.
[http://dx.doi.org/10.1083/jcb.200501085] [PMID: 15911875]
[125]
Shi, Y.; Lin, S.; Staats, K.A.; Li, Y.; Chang, W.H.; Hung, S.T.; Hendricks, E.; Linares, G.R.; Wang, Y.; Son, E.Y.; Wen, X.; Kisler, K.; Wilkinson, B.; Menendez, L.; Sugawara, T.; Woolwine, P.; Huang, M.; Cowan, M.J.; Ge, B.; Koutsodendris, N.; Sandor, K.P.; Komberg, J.; Vangoor, V.R.; Senthilkumar, K.; Hennes, V.; Seah, C.; Nelson, A.R.; Cheng, T.Y.; Lee, S.J.J.; August, P.R.; Chen, J.A.; Wisniewski, N.; Hanson-Smith, V.; Belgard, T.G.; Zhang, A.; Coba, M.; Grunseich, C.; Ward, M.E.; van den Berg, L.H.; Pasterkamp, R.J.; Trotti, D.; Zlokovic, B.V.; Ichida, J.K. Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons. Nat. Med., 2018, 24(3), 313-325.
[http://dx.doi.org/10.1038/nm.4490] [PMID: 29400714]
[126]
Slowicka, K.; Vereecke, L.; van Loo, G. Cellular functions of optineurin in health and disease. Trends Immunol., 2016, 37(9), 621-633.
[http://dx.doi.org/10.1016/j.it.2016.07.002] [PMID: 27480243]
[127]
Rademakers, R.; van Blitterswijk, M. Excess of rare damaging TUBA4A variants suggests cytoskeletal defects in ALS. Neuron, 2014, 84(2), 241-243.
[http://dx.doi.org/10.1016/j.neuron.2014.10.002] [PMID: 25374348]
[128]
Laird, F.M.; Farah, M.H.; Ackerley, S.; Hoke, A.; Maragakis, N.; Rothstein, J.D.; Griffin, J.; Price, D.L.; Martin, L.J.; Wong, P.C. Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking. J. Neurosci., 2008, 28(9), 1997-2005.
[http://dx.doi.org/10.1523/JNEUROSCI.4231-07.2008] [PMID: 18305234]
[129]
Nicolas, A.; Kenna, K.P.; Renton, A.E.; Ticozzi, N.; Faghri, F.; Chia, R.; Dominov, J.A.; Kenna, B.J.; Nalls, M.A.; Keagle, P.; Rivera, A.M.; van Rheenen, W.; Murphy, N.A.; van Vugt, J.J.F.A.; Geiger, J.T.; Van der Spek, R.A.; Pliner, H.A. Shankaracharya; Smith, B.N.; Marangi, G.; Topp, S.D.; Abramzon, Y.; Gkazi, A.S.; Eicher, J.D.; Kenna, A.; Mora, G.; Calvo, A.; Mazzini, L.; Riva, N.; Mandrioli, J.; Caponnetto, C.; Battistini, S.; Volanti, P.; La Bella, V.; Conforti, F.L.; Borghero, G.; Messina, S.; Simone, I.L.; Trojsi, F.; Salvi, F.; Logullo, F.O.; D’Alfonso, S.; Corrado, L.; Capasso, M.; Ferrucci, L.; Moreno, C.A.M.; Kamalakaran, S.; Goldstein, D.B.; Gitler, A.D.; Harris, T.; Myers, R.M.; Phatnani, H.; Musunuri, R.L.; Evani, U.S.; Abhyankar, A.; Zody, M.C.; Kaye, J.; Finkbeiner, S.; Wyman, S.K.; LeNail, A.; Lima, L.; Fraenkel, E.; Svendsen, C.N.; Thompson, L.M.; Van Eyk, J.E.; Berry, J.D.; Miller, T.M.; Kolb, S.J.; Cudkowicz, M.; Baxi, E.; Benatar, M.; Taylor, J.P.; Rampersaud, E.; Wu, G.; Wuu, J.; Lauria, G.; Verde, F.; Fogh, I.; Tiloca, C.; Comi, G.P.; Sorarù, G.; Cereda, C.; Corcia, P.; Laaksovirta, H.; Myllykangas, L.; Jansson, L.; Valori, M.; Ealing, J.; Hamdalla, H.; Rollinson, S.; Pickering-Brown, S.; Orrell, R.W.; Sidle, K.C.; Malaspina, A.; Hardy, J.; Singleton, A.B.; Johnson, J.O.; Arepalli, S.; Sapp, P.C.; McKenna-Yasek, D.; Polak, M.; Asress, S.; Al-Sarraj, S.; King, A.; Troakes, C.; Vance, C.; de Belleroche, J.; Baas, F.; ten Asbroek, A.L.M.A.; Muñoz-Blanco, J.L.; Hernandez, D.G.; Ding, J.; Gibbs, J.R.; Scholz, S.W.; Floeter, M.K.; Campbell, R.H.; Landi, F.; Bowser, R.; Pulst, S.M.; Ravits, J.M.; MacGowan, D.J.L.; Kirby, J.; Pioro, E.P.; Pamphlett, R.; Broach, J.; Gerhard, G.; Dunckley, T.L.; Brady, C.B.; Kowall, N.W.; Troncoso, J.C.; Le Ber, I.; Mouzat, K.; Lumbroso, S.; Heiman-Patterson, T.D.; Kamel, F.; Van Den Bosch, L.; Baloh, R.H.; Strom, T.M.; Meitinger, T.; Shatunov, A.; Van Eijk, K.R.; de Carvalho, M.; Kooyman, M.; Middelkoop, B.; Moisse, M.; McLaughlin, R.L.; Van Es, M.A.; Weber, M.; Boylan, K.B.; Van Blitterswijk, M.; Rademakers, R.; Morrison, K.E.; Basak, A.N.; Mora, J.S.; Drory, V.E.; Shaw, P.J.; Turner, M.R.; Talbot, K.; Hardiman, O.; Williams, K.L.; Fifita, J.A.; Nicholson, G.A.; Blair, I.P.; Rouleau, G.A.; Esteban-Pérez, J.; García-Redondo, A.; Al-Chalabi, A.; Rogaeva, E.; Zinman, L.; Ostrow, L.W.; Maragakis, N.J.; Rothstein, J.D.; Simmons, Z.; Cooper-Knock, J.; Brice, A.; Goutman, S.A.; Feldman, E.L.; Gibson, S.B.; Taroni, F.; Ratti, A.; Gellera, C.; Van Damme, P.; Robberecht, W.; Fratta, P.; Sabatelli, M.; Lunetta, C.; Ludolph, A.C.; Andersen, P.M.; Weishaupt, J.H.; Camu, W.; Trojanowski, J.Q.; Van Deerlin, V.M.; Brown, R.H., Jr; van den Berg, L.H.; Veldink, J.H.; Harms, M.B.; Glass, J.D.; Stone, D.J.; Tienari, P.; Silani, V.; Chiò, A.; Shaw, C.E.; Traynor, B.J.; Landers, J.E.; Logullo, F.O.; Simone, I.; Logroscino, G.; Salvi, F.; Bartolomei, I.; Borghero, G.; Murru, M.R.; Costantino, E.; Pani, C.; Puddu, R.; Caredda, C.; Piras, V.; Tranquilli, S.; Cuccu, S.; Corongiu, D.; Melis, M.; Milia, A.; Marrosu, F.; Marrosu, M.G.; Floris, G.; Cannas, A.; Tranquilli, S.; Capasso, M.; Caponnetto, C.; Mancardi, G.; Origone, P.; Mandich, P.; Conforti, F.L.; Cavallaro, S.; Mora, G.; Marinou, K.; Sideri, R.; Penco, S.; Mosca, L.; Lunetta, C.; Pinter, G.L.; Corbo, M.; Riva, N.; Carrera, P.; Volanti, P.; Mandrioli, J.; Fini, N.; Fasano, A.; Tremolizzo, L.; Arosio, A.; Ferrarese, C.; Trojsi, F.; Tedeschi, G.; Monsurrò, M.R.; Piccirillo, G.; Femiano, C.; Ticca, A.; Ortu, E.; La Bella, V.; Spataro, R.; Colletti, T.; Sabatelli, M.; Zollino, M.; Conte, A.; Luigetti, M.; Lattante, S.; Marangi, G.; Santarelli, M.; Petrucci, A.; Pugliatti, M.; Pirisi, A.; Parish, L.D.; Occhineri, P.; Giannini, F.; Battistini, S.; Ricci, C.; Benigni, M.; Cau, T.B.; Loi, D.; Calvo, A.; Moglia, C.; Brunetti, M.; Barberis, M.; Restagno, G.; Casale, F.; Marrali, G.; Fuda, G.; Ossola, I.; Cammarosano, S.; Canosa, A.; Ilardi, A.; Manera, U.; Grassano, M.; Tanel, R.; Pisano, F.; Harms, M.B.; Goldstein, D.B.; Shneider, N.A.; Goutman, S.; Simmons, Z.; Miller, T.M.; Chandran, S.; Pal, S.; Manousakis, G.; Appel, S.H.; Simpson, E.; Wang, L.; Baloh, R.H.; Gibson, S.; Bedlack, R.; Lacomis, D.; Sareen, D.; Sherman, A.; Bruijn, L.; Penny, M.; Allen, A.S.; Appel, S.; Baloh, R.H.; Bedlack, R.S.; Boone, B.E.; Brown, R.; Carulli, J.P.; Chesi, A.; Chung, W.K.; Cirulli, E.T.; Cooper, G.M.; Couthouis, J.; Day-Williams, A.G.; Dion, P.A.; Gibson, S.; Gitler, A.D.; Glass, J.D.; Goldstein, D.B.; Han, Y.; Harms, M.B.; Harris, T.; Hayes, S.D.; Jones, A.L.; Keebler, J.; Krueger, B.J.; Lasseigne, B.N.; Levy, S.E.; Lu, Y-F.; Maniatis, T.; McKenna-Yasek, D.; Miller, T.M.; Myers, R.M.; Petrovski, S.; Pulst, S.M.; Raphael, A.R.; Ravits, J.M.; Ren, Z.; Rouleau, G.A.; Sapp, P.C.; Shneider, N.A.; Simpson, E.; Sims, K.B.; Staropoli, J.F.; Waite, L.L.; Wang, Q.; Wimbish, J.R.; Xin, W.W.; Phatnani, H.; Kwan, J.; Sareen, D.; Broach, J.R.; Simmons, Z.; Arcila-Londono, X.; Lee, E.B.; Van Deerlin, V.M.; Shneider, N.A.; Fraenkel, E.; Ostrow, L.W.; Baas, F.; Zaitlen, N.; Berry, J.D.; Malaspina, A.; Fratta, P.; Cox, G.A.; Thompson, L.M.; Finkbeiner, S.; Dardiotis, E.; Miller, T.M.; Chandran, S.; Pal, S.; Hornstein, E.; MacGowan, D.J.; Heiman-Patterson, T.; Hammell, M.G.; Patsopoulos, N.A.; Dubnau, J.; Nath, A.; Kaye, J.; Finkbeiner, S.; Wyman, S.; LeNail, A.; Lima, L.; Fraenkel, E.; Rothstein, J.D.; Svendsen, C.N.; Thompson, L.M.; Van Eyk, J.; Maragakis, N.J.; Berry, J.D.; Glass, J.D.; Miller, T.M.; Kolb, S.J.; Baloh, R.H.; Cudkowicz, M.; Baxi, E.; Benatar, M.; Taylor, J.P.; Wu, G.; Rampersaud, E.; Wuu, J.; Rademakers, R.; Züchner, S.; Schule, R.; McCauley, J.; Hussain, S.; Cooley, A.; Wallace, M.; Clayman, C.; Barohn, R.; Statland, J.; Ravits, J.; Swenson, A.; Jackson, C.; Trivedi, J.; Khan, S.; Katz, J.; Jenkins, L.; Burns, T.; Gwathmey, K.; Caress, J.; McMillan, C.; Elman, L.; Pioro, E.; Heckmann, J.; So, Y.; Walk, D.; Maiser, S.; Zhang, J.; Silani, V.; Ticozzi, N.; Gellera, C.; Ratti, A.; Taroni, F.; Lauria, G.; Verde, F.; Fogh, I.; Tiloca, C.; Comi, G.P.; Sorarù, G.; Cereda, C.; D’Alfonso, S.; Corrado, L.; De Marchi, F.; Corti, S.; Ceroni, M.; Mazzini, L.; Siciliano, G.; Filosto, M.; Inghilleri, M.; Peverelli, S.; Colombrita, C.; Poletti, B.; Maderna, L.; Del Bo, R.; Gagliardi, S.; Querin, G.; Bertolin, C.; Pensato, V.; Castellotti, B.; Camu, W.; Mouzat, K.; Lumbroso, S.; Corcia, P.; Meininger, V.; Besson, G.; Lagrange, E.; Clavelou, P.; Guy, N.; Couratier, P.; Vourch, P.; Danel, V.; Bernard, E.; Lemasson, G.; Al Kheifat, A.; Al-Chalabi, A.; Andersen, P.; Basak, A.N.; Blair, I.P.; Chio, A.; Cooper-Knock, J.; Corcia, P.; Couratier, P.; de Carvalho, M.; Dekker, A.; Drory, V.; Redondo, A.G.; Gotkine, M.; Hardiman, O.; Hide, W.; Iacoangeli, A.; Glass, J.; Kenna, K.; Kiernan, M.; Kooyman, M.; Landers, J.; McLaughlin, R.; Middelkoop, B.; Mill, J.; Neto, M.M.; Moisse, M.; Pardina, J.M.; Morrison, K.; Newhouse, S.; Pinto, S.; Pulit, S.; Robberecht, W.; Shatunov, A.; Shaw, P.; Shaw, C.; Silani, V.; Sproviero, W.; Tazelaar, G.; Ticozzi, N.; van Damme, P.; van den Berg, L.; van der Spek, R.; van Eijk, K.; van Es, M.; van Rheenen, W.; van Vugt, J.; Veldink, J.; Weber, M.; Williams, K.L.; Zatz, M.; Bauer, D.C.; Twine, N.A. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron, 2018, 97(6), 1268-1283.e6.
[http://dx.doi.org/10.1016/j.neuron.2018.02.027] [PMID: 29566793]
[130]
Ackerley, S.; Grierson, A.J.; Banner, S.; Perkinton, M.S.; Brownlees, J.; Byers, H.L.; Ward, M.; Thornhill, P.; Hussain, K.; Waby, J.S.; Anderton, B.H.; Cooper, J.D.; Dingwall, C.; Leigh, P.N.; Shaw, C.E.; Miller, C.C.J. p38α stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis. Mol. Cell. Neurosci., 2004, 26(2), 354-364.
[http://dx.doi.org/10.1016/j.mcn.2004.02.009] [PMID: 15207859]
[131]
Brownlees, J.; Yates, A.; Bajaj, N.P.; Davis, D.; Anderton, B.H.; Leigh, P.N. Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3. J. Cell Sci., 2000, 113(Pt 3), 401-407.
[http://dx.doi.org/10.1242/jcs.113.3.401]
[132]
Deshpande, M.; Feiger, Z.; Shilton, A.K.; Luo, C.C.; Silverman, E.; Rodal, A.A. Role of BMP receptor traffic in synaptic growth defects in an ALS model. Mol. Biol. Cell, 2016, 27(19), 2898-2910.
[http://dx.doi.org/10.1091/mbc.E16-07-0519] [PMID: 27535427]
[133]
Aoki, Y.; Manzano, R.; Lee, Y.; Dafinca, R.; Aoki, M.; Douglas, A.G.L.; Varela, M.A.; Sathyaprakash, C.; Scaber, J.; Barbagallo, P.; Vader, P.; Mäger, I.; Ezzat, K.; Turner, M.R.; Ito, N.; Gasco, S.; Ohbayashi, N.; El Andaloussi, S.; Takeda, S.; Fukuda, M.; Talbot, K.; Wood, M.J.A. C9orf72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementia. Brain, 2017, 140(4), 887-897.
[http://dx.doi.org/10.1093/brain/awx024] [PMID: 28334866]
[134]
Zhen, Y.; Stenmark, H. Cellular functions of Rab GTPases at a glance. J. Cell Sci., 2015, 128(17), jcs.166074.
[http://dx.doi.org/10.1242/jcs.166074] [PMID: 26272922]
[135]
Lai, C.; Xie, C.; McCormack, S.G.; Chiang, H.C.; Michalak, M.K.; Lin, X.; Chandran, J.; Shim, H.; Shimoji, M.; Cookson, M.R.; Huganir, R.L.; Rothstein, J.D.; Price, D.L.; Wong, P.C.; Martin, L.J.; Zhu, J.J.; Cai, H. Amyotrophic lateral sclerosis 2-deficiency leads to neuronal degeneration in amyotrophic lateral sclerosis through altered AMPA receptor trafficking. J. Neurosci., 2006, 26(45), 11798-11806.
[http://dx.doi.org/10.1523/JNEUROSCI.2084-06.2006] [PMID: 17093100]
[136]
Ritson, G.P.; Custer, S.K.; Freibaum, B.D.; Guinto, J.B.; Geffel, D.; Moore, J.; Tang, W.; Winton, M.J.; Neumann, M.; Trojanowski, J.Q.; Lee, V.M.Y.; Forman, M.S.; Taylor, J.P. TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J. Neurosci., 2010, 30(22), 7729-7739.
[http://dx.doi.org/10.1523/JNEUROSCI.5894-09.2010] [PMID: 20519548]
[137]
Gwon, Y.; Maxwell, B.A.; Kolaitis, R.M.; Zhang, P.; Kim, H.J.; Taylor, J.P. Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner. Science, 2021, 372(6549), eabf6548.
[http://dx.doi.org/10.1126/science.abf6548] [PMID: 34739333]
[138]
Bertolin, C.; Querin, G.; Bozzoni, V.; Martinelli, I.; De Bortoli, M.; Rampazzo, A.; Gellera, C.; Pegoraro, E.; Sorarù, G. NewFIG 4 gene mutations causing aggressive ALS. Eur. J. Neurol., 2018, 25(3), e41-e42.
[http://dx.doi.org/10.1111/ene.13559] [PMID: 29464931]
[139]
Zhang, K.; Daigle, J.G.; Cunningham, K.M.; Coyne, A.N.; Ruan, K.; Grima, J.C.; Bowen, K.E.; Wadhwa, H.; Yang, P.; Rigo, F.; Taylor, J.P.; Gitler, A.D.; Rothstein, J.D.; Lloyd, T.E. Stress granule assembly disrupts nucleocytoplasmic transport. Cell, 2018, 173(4), 958-971.e17.
[http://dx.doi.org/10.1016/j.cell.2018.03.025] [PMID: 29628143]
[140]
Ederle, H.; Funk, C.; Abou-Ajram, C.; Hutten, S.; Funk, E.B.E.; Kehlenbach, R.H.; Bailer, S.M.; Dormann, D. Nuclear egress of TDP-43 and FUS occurs independently of Exportin-1/CRM1. Sci. Rep., 2018, 8(1), 7084.
[http://dx.doi.org/10.1038/s41598-018-25007-5] [PMID: 29728564]
[141]
Ciryam, P.; Antalek, M.; Cid, F.; Tartaglia, G.G.; Dobson, C.M.; Guettsches, A.K.; Eggers, B.; Vorgerd, M.; Marcus, K.; Kley, R.A.; Morimoto, R.I.; Vendruscolo, M.; Weihl, C.C. A metastable subproteome underlies inclusion formation in muscle proteinopathies. Acta Neuropathol. Commun., 2019, 7(1), 197.
[http://dx.doi.org/10.1186/s40478-019-0853-9] [PMID: 31796104]
[142]
Yerbury, J.J.; Farrawell, N.E.; McAlary, L. Proteome homeostasis dysfunction: A unifying principle in ALS pathogenesis. Trends Neurosci., 2020, 43(5), 274-284.
[http://dx.doi.org/10.1016/j.tins.2020.03.002] [PMID: 32353332]
[143]
Medinas, D.B.; Valenzuela, V.; Hetz, C. Proteostasis disturbance in amyotrophic lateral sclerosis. Hum. Mol. Genet., 2017, 26(R2), R91-R104.
[http://dx.doi.org/10.1093/hmg/ddx274] [PMID: 28977445]
[144]
Bendotti, C.; Marino, M.; Cheroni, C.; Fontana, E.; Crippa, V.; Poletti, A.; De Biasi, S. Dysfunction of constitutive and inducible ubiquitin-proteasome system in amyotrophic lateral sclerosis: Implication for protein aggregation and immune response. Prog. Neurobiol., 2012, 97(2), 101-126.
[http://dx.doi.org/10.1016/j.pneurobio.2011.10.001] [PMID: 22033150]
[145]
Ramesh, N.; Pandey, U.B. Autophagy dysregulation in ALS: When protein aggregates get out of hand. Front. Mol. Neurosci., 2017, 10, 263.
[http://dx.doi.org/10.3389/fnmol.2017.00263] [PMID: 28878620]
[146]
Prasad, A.; Bharathi, V.; Sivalingam, V.; Girdhar, A.; Patel, B.K. Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis. Front. Mol. Neurosci., 2019, 12, 25.
[http://dx.doi.org/10.3389/fnmol.2019.00025] [PMID: 30837838]
[147]
Ivanova, M.I.; Sievers, S.A.; Guenther, E.L.; Johnson, L.M.; Winkler, D.D.; Galaleldeen, A. Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS. Proc. Natl. Acad. Sci., 2014, 111, 197.
[http://dx.doi.org/10.1073/pnas.1320786110]
[148]
Deng, H.X.; Zhai, H.; Bigio, E.H.; Yan, J.; Fecto, F.; Ajroud, K.; Mishra, M.; Ajroud-Driss, S.; Heller, S.; Sufit, R.; Siddique, N.; Mugnaini, E.; Siddique, T. FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann. Neurol., 2010, 67(6), NA.
[http://dx.doi.org/10.1002/ana.22051] [PMID: 20517935]
[149]
Pokrishevsky, E.; Grad, L.I.; Yousefi, M.; Wang, J.; Mackenzie, I.R.; Cashman, N.R. Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis. PLoS One, 2012, 7(4), e35050.
[http://dx.doi.org/10.1371/journal.pone.0035050] [PMID: 22493728]
[150]
Williams, K.L.; Warraich, S.T.; Yang, S.; Solski, J.A.; Fernando, R.; Rouleau, G.A.; Nicholson, G.A.; Blair, I.P. UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis. Neurobiol. Aging, 2012, 33(10), 2527.e3-2527.e10.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.05.008] [PMID: 22717235]
[151]
Schmitz, A.; Pinheiro, M.J.; Oertig, I.; Maharjan, N.; Saxena, S. Emerging perspectives on dipeptide repeat proteins in C9ORF72 ALS/FTD. Front. Cell. Neurosci., 2021, 15, 637548.
[http://dx.doi.org/10.3389/fncel.2021.637548] [PMID: 33679328]
[152]
Gafson, A.R.; Barthélemy, N.R.; Bomont, P.; Carare, R.O.; Durham, H.D.; Julien, J.P.; Kuhle, J.; Leppert, D.; Nixon, R.A.; Weller, R.O.; Zetterberg, H.; Matthews, P.M. Neurofilaments: neurobiological foundations for biomarker applications. Brain, 2020, 143(7), 1975-1998.
[http://dx.doi.org/10.1093/brain/awaa098] [PMID: 32408345]
[153]
Kabashi, E.; Agar, J.N.; Strong, M.J.; Durham, H.D. Impaired proteasome function in sporadic amyotrophic lateral sclerosis. Amyotroph. Lateral Scler., 2012, 13(4), 367-371.
[http://dx.doi.org/10.3109/17482968.2012.686511] [PMID: 22632443]
[154]
Cheroni, C.; Marino, M.; Tortarolo, M.; Veglianese, P.; De Biasi, S.; Fontana, E.; Zuccarello, L.V.; Maynard, C.J.; Dantuma, N.P.; Bendotti, C. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis. Hum. Mol. Genet., 2009, 18(1), 82-96.
[http://dx.doi.org/10.1093/hmg/ddn319] [PMID: 18826962]
[155]
Kabashi, E.; Agar, J.N.; Taylor, D.M.; Minotti, S.; Durham, H.D. Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis. J. Neurochem., 2004, 89(6), 1325-1335.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02453.x] [PMID: 15189335]
[156]
Kitajima, Y.; Yoshioka, K.; Suzuki, N. The ubiquitin–proteasome system in regulation of the skeletal muscle homeostasis and atrophy: from basic science to disorders. J. Physiol. Sci., 2020, 70(1), 40.
[http://dx.doi.org/10.1186/s12576-020-00768-9] [PMID: 32938372]
[157]
Barthelme, D.; Jauregui, R.; Sauer, R.T. An ALS disease mutation in Cdc48/p97 impairs 20S proteasome binding and proteolytic communication. Protein Sci., 2015, 24(9), 1521-1527.
[http://dx.doi.org/10.1002/pro.2740] [PMID: 26134898]
[158]
Le, N.T.T.; Chang, L.; Kovlyagina, I.; Georgiou, P.; Safren, N.; Braunstein, K.E.; Kvarta, M.D.; Van Dyke, A.M.; LeGates, T.A.; Philips, T.; Morrison, B.M.; Thompson, S.M.; Puche, A.C.; Gould, T.D.; Rothstein, J.D.; Wong, P.C.; Monteiro, M.J. Motor neuron disease, TDP-43 pathology, and memory deficits in mice expressing ALS–FTD-linked UBQLN2 mutations. Proc. Natl. Acad. Sci. USA, 2016, 113(47), E7580-E7589.
[http://dx.doi.org/10.1073/pnas.1608432113] [PMID: 27834214]
[159]
Williams, K.L.; Topp, S.; Yang, S.; Smith, B.; Fifita, J.A.; Warraich, S.T.; Zhang, K.Y.; Farrawell, N.; Vance, C.; Hu, X.; Chesi, A.; Leblond, C.S.; Lee, A.; Rayner, S.L.; Sundaramoorthy, V.; Dobson-Stone, C.; Molloy, M.P.; van Blitterswijk, M.; Dickson, D.W.; Petersen, R.C.; Graff-Radford, N.R.; Boeve, B.F.; Murray, M.E.; Pottier, C.; Don, E.; Winnick, C.; McCann, E.P.; Hogan, A.; Daoud, H.; Levert, A.; Dion, P.A.; Mitsui, J.; Ishiura, H.; Takahashi, Y.; Goto, J.; Kost, J.; Gellera, C.; Gkazi, A.S.; Miller, J.; Stockton, J.; Brooks, W.S.; Boundy, K.; Polak, M.; Muñoz-Blanco, J.L.; Esteban-Pérez, J.; Rábano, A.; Hardiman, O.; Morrison, K.E.; Ticozzi, N.; Silani, V.; de Belleroche, J.; Glass, J.D.; Kwok, J.B.J.; Guillemin, G.J.; Chung, R.S.; Tsuji, S.; Brown, R.H., Jr; García-Redondo, A.; Rademakers, R.; Landers, J.E.; Gitler, A.D.; Rouleau, G.A.; Cole, N.J.; Yerbury, J.J.; Atkin, J.D.; Shaw, C.E.; Nicholson, G.A.; Blair, I.P. CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia. Nat. Commun., 2016, 7(1), 11253.
[http://dx.doi.org/10.1038/ncomms11253] [PMID: 27080313]
[160]
Ling, S.C.; Polymenidou, M.; Cleveland, D.W. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron, 2013, 79(3), 416-438.
[http://dx.doi.org/10.1016/j.neuron.2013.07.033] [PMID: 23931993]
[161]
Dudman, J.; Qi, X. Stress Granule Dysregulation in Amyotrophic Lateral Sclerosis. Front. Cell. Neurosci., 2020, 14, 598517.
[http://dx.doi.org/10.3389/fncel.2020.598517] [PMID: 33281563]
[162]
McAlary, L.; Plotkin, S.S.; Yerbury, J.J.; Cashman, N.R. Prion-like propagation of protein misfolding and aggregation in amyotrophic lateral sclerosis. Front. Mol. Neurosci., 2019, 12, 262.
[http://dx.doi.org/10.3389/fnmol.2019.00262] [PMID: 31736708]
[163]
Nolan, M.; Talbot, K.; Ansorge, O. Pathogenesis of FUS-associated ALS and FTD: insights from rodent models. Acta Neuropathol. Commun., 2016, 4(1), 99.
[http://dx.doi.org/10.1186/s40478-016-0358-8] [PMID: 27600654]
[164]
Kitamura, A.; Nakayama, Y.; Shibasaki, A.; Taki, A.; Yuno, S.; Takeda, K.; Yahara, M.; Tanabe, N.; Kinjo, M. Interaction of RNA with a C-terminal fragment of the amyotrophic lateral sclerosis-associated TDP43 reduces cytotoxicity. Sci. Rep., 2016, 6(1), 19230.
[http://dx.doi.org/10.1038/srep19230] [PMID: 26757674]
[165]
Birsa, N.; Bentham, M.P.; Fratta, P. Cytoplasmic functions of TDP-43 and FUS and their role in ALS. Semin. Cell Dev. Biol., 2020, 99, 193-201.
[http://dx.doi.org/10.1016/j.semcdb.2019.05.023] [PMID: 31132467]
[166]
Ratti, A.; Buratti, E. Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins. J. Neurochem., 2016, 138(Suppl. 1), 95-111.
[http://dx.doi.org/10.1111/jnc.13625] [PMID: 27015757]
[167]
Balendra, R.; Isaacs, A.M. C9orf72-mediated ALS and FTD: multiple pathways to disease. Nat. Rev. Neurol., 2018, 14(9), 544-558.
[http://dx.doi.org/10.1038/s41582-018-0047-2] [PMID: 30120348]
[168]
Tang, X.; Toro, A. T G, S.; Gao, J.; Chalk, J.; Oskarsson, B.; Zhang, K. Divergence, convergence, and therapeutic implications: A cell biology perspective of C9ORF72-ALS/FTD. Mol. Neurodegener., 2020, 15(1), 34.
[http://dx.doi.org/10.1186/s13024-020-00383-7] [PMID: 32513219]
[169]
Ayaki, T.; Ito, H.; Komure, O.; Kamada, M.; Nakamura, M.; Wate, R.; Kusaka, H.; Yamaguchi, Y.; Li, F.; Kawakami, H.; Urushitani, M.; Takahashi, R. Multiple proteinopathies in familial ALS cases with optineurin mutations. J. Neuropathol. Exp. Neurol., 2018, 77(2), 128-138.
[http://dx.doi.org/10.1093/jnen/nlx109] [PMID: 29272468]
[170]
Münch, C.; O’Brien, J. Bertolotti, A Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells. Proc. Natl. Acad. Sci., 2011, 108(9), 3548-3553.
[http://dx.doi.org/10.1073/pnas.1017275108]
[171]
Geser, F.; Brandmeir, N.J.; Kwong, L.K.; Martinez-Lage, M.; Elman, L.; McCluskey, L.; Xie, S.X.; Lee, V.M.Y.; Trojanowski, J.Q. Evidence of multisystem disorder in whole-brain map of pathological TDP-43 in amyotrophic lateral sclerosis. Arch. Neurol., 2008, 65(5), 636-641.
[http://dx.doi.org/10.1001/archneur.65.5.636] [PMID: 18474740]
[172]
Sun, Y.; Curle, A.J.; Haider, A.M.; Balmus, G. The role of DNA damage response in amyotrophic lateral sclerosis. Essays Biochem., 2020, 64(5), 847-861.
[http://dx.doi.org/10.1042/EBC20200002] [PMID: 33078197]
[173]
Hewitt, G.; Carroll, B.; Sarallah, R.; Correia-Melo, C.; Ogrodnik, M.; Nelson, G.; Otten, E.G.; Manni, D.; Antrobus, R.; Morgan, B.A.; von Zglinicki, T.; Jurk, D.; Seluanov, A.; Gorbunova, V.; Johansen, T.; Passos, J.F.; Korolchuk, V.I. SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair. Autophagy, 2016, 12(10), 1917-1930.
[http://dx.doi.org/10.1080/15548627.2016.1210368] [PMID: 27391408]
[174]
Konopka, A.; Whelan, D.R.; Jamali, M.S.; Perri, E.; Shahheydari, H.; Toth, R.P.; Parakh, S.; Robinson, T.; Cheong, A.; Mehta, P.; Vidal, M.; Ragagnin, A.M.G.; Khizhnyak, I.; Jagaraj, C.J.; Galper, J.; Grima, N.; Deva, A.; Shadfar, S.; Nicholson, G.A.; Yang, S.; Cutts, S.M.; Horejsi, Z.; Bell, T.D.M.; Walker, A.K.; Blair, I.P.; Atkin, J.D. Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations. Mol. Neurodegener., 2020, 15(1), 51.
[http://dx.doi.org/10.1186/s13024-020-00386-4] [PMID: 32907630]
[175]
Wang, H.; Guo, W.; Mitra, J.; Hegde, P.M.; Vandoorne, T.; Eckelmann, B.J.; Mitra, S.; Tomkinson, A.E.; Van Den Bosch, L.; Hegde, M.L. Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis. Nat. Commun., 2018, 9(1), 3683.
[http://dx.doi.org/10.1038/s41467-018-06111-6] [PMID: 30206235]
[176]
Kawaguchi, T.; Rollins, M.G.; Moinpour, M.; Morera, A.A.; Ebmeier, C.C.; Old, W.M.; Schwartz, J.C. Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage. J. Proteome Res., 2020, 19(1), 360-370.
[http://dx.doi.org/10.1021/acs.jproteome.9b00575] [PMID: 31693373]
[177]
Haeusler, A.R.; Donnelly, C.J.; Periz, G.; Simko, E.A.J.; Shaw, P.G.; Kim, M.S.; Maragakis, N.J.; Troncoso, J.C.; Pandey, A.; Sattler, R.; Rothstein, J.D.; Wang, J. C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature, 2014, 507(7491), 195-200.
[http://dx.doi.org/10.1038/nature13124] [PMID: 24598541]
[178]
Farg, M.A.; Konopka, A.; Soo, K.Y.; Ito, D.; Atkin, J.D. The DNA damage response (DDR) is induced by the C9orf72 repeat expansion in amyotrophic lateral sclerosis. Hum. Mol. Genet., 2017, 26(15), 2882-2896.
[http://dx.doi.org/10.1093/hmg/ddx170] [PMID: 28481984]
[179]
Nihei, Y.; Mori, K.; Werner, G.; Arzberger, T.; Zhou, Q.; Khosravi, B.; Japtok, J.; Hermann, A.; Sommacal, A.; Weber, M.; Kamp, F.; Nuscher, B.; Edbauer, D.; Haass, C. Poly-glycine–alanine exacerbates C9orf72 repeat expansion-mediated DNA damage via sequestration of phosphorylated ATM and loss of nuclear hnRNPA3. Acta Neuropathol., 2020, 139(1), 99-118.
[http://dx.doi.org/10.1007/s00401-019-02082-0] [PMID: 31642962]
[180]
Kok, J.R.; Palminha, N.M.; Dos Santos Souza, C.; El-Khamisy, S.F.; Ferraiuolo, L. DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity. Cell. Mol. Life Sci., 2021, 78(15), 5707-5729.
[http://dx.doi.org/10.1007/s00018-021-03872-0] [PMID: 34173837]
[181]
Zhang, Y.J.; Guo, L.; Gonzales, P.K.; Gendron, T.F.; Wu, Y.; Jansen-West, K.; O’Raw, A.D.; Pickles, S.R.; Prudencio, M.; Carlomagno, Y.; Gachechiladze, M.A.; Ludwig, C.; Tian, R.; Chew, J.; DeTure, M.; Lin, W.L.; Tong, J.; Daughrity, L.M.; Yue, M.; Song, Y.; Andersen, J.W.; Castanedes-Casey, M.; Kurti, A.; Datta, A.; Antognetti, G.; McCampbell, A.; Rademakers, R.; Oskarsson, B.; Dickson, D.W.; Kampmann, M.; Ward, M.E.; Fryer, J.D.; Link, C.D.; Shorter, J.; Petrucelli, L. Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity. Science, 2019, 363(6428), eaav2606.
[http://dx.doi.org/10.1126/science.aav2606] [PMID: 30765536]
[182]
Tanaka, Y.; Chen, Z.J. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci. Signal., 2012, 5(214), ra20.
[http://dx.doi.org/10.1126/scisignal.2002521] [PMID: 22394562]
[183]
Tadic, V.; Prell, T.; Lautenschlaeger, J.; Grosskreutz, J. The ER mitochondria calcium cycle and ER stress response as therapeutic targets in amyotrophic lateral sclerosis. Front. Cell. Neurosci., 2014, 8, 147.
[http://dx.doi.org/10.3389/fncel.2014.00147] [PMID: 24910594]
[184]
Stoica, R.; Paillusson, S.; Gomez-Suaga, P.; Mitchell, J.C.; Lau, D.H.W.; Gray, E.H.; Sancho, R.M.; Vizcay-Barrena, G.; De Vos, K.J.; Shaw, C.E.; Hanger, D.P.; Noble, W.; Miller, C.C.J. ALS/FTD ‐associated FUS activates GSK ‐3β to disrupt the VAPB – PTPIP 51 interaction and ER –mitochondria associations. EMBO Rep., 2016, 17(9), 1326-1342.
[http://dx.doi.org/10.15252/embr.201541726] [PMID: 27418313]
[185]
Vicencio, E.; Beltrán, S.; Labrador, L.; Manque, P.; Nassif, M.; Woehlbier, U. Implications of selective autophagy dysfunction for ALS pathology. Cells, 2020, 9(2), 381.
[http://dx.doi.org/10.3390/cells9020381] [PMID: 32046060]
[186]
Sprenkle, N.T.; Sims, S.G.; Sánchez, C.L.; Meares, G.P. Endoplasmic reticulum stress and inflammation in the central nervous system. Mol. Neurodegener., 2017, 12(1), 42.
[http://dx.doi.org/10.1186/s13024-017-0183-y] [PMID: 28545479]
[187]
Lee, D.Y.; Jeon, G.S.; Sung, J.J. ALS-Linked Mutant SOD1 associates with TIA-1 and alters stress granule dynamics. Neurochem. Res., 2020, 45(12), 2884-2893.
[http://dx.doi.org/10.1007/s11064-020-03137-5] [PMID: 33025330]
[188]
Matus, S.; Valenzuela, V.; Medinas, D.B.; Hetz, C. Er dysfunction and protein folding stress in ALS. Int. J. Cell Biol., 2013, 2013, 1-12.
[http://dx.doi.org/10.1155/2013/674751] [PMID: 24324498]
[189]
Perri, E.; Parakh, S.; Atkin, J. Protein Disulphide Isomerases: emerging roles of PDI and ERp57 in the nervous system and as therapeutic targets for ALS. Expert Opin. Ther. Targets, 2017, 21(1), 37-49.
[http://dx.doi.org/10.1080/14728222.2016.1254197] [PMID: 27786579]
[190]
Wang, L.; Popko, B.; Roos, R.P. The unfolded protein response in familial amyotrophic lateral sclerosis. Hum. Mol. Genet., 2011, 20(5), 1008-1015.
[http://dx.doi.org/10.1093/hmg/ddq546] [PMID: 21159797]
[191]
Borgese, N.; Iacomino, N.; Colombo, S.F.; Navone, F. The Link between VAPB loss of function and amyotrophic lateral sclerosis. Cells, 2021, 10(8), 1865.
[http://dx.doi.org/10.3390/cells10081865] [PMID: 34440634]
[192]
Sundaramoorthy, V.; Sultana, J.M.; Atkin, J.D. Golgi fragmentation in amyotrophic lateral sclerosis, an overview of possible triggers and consequences. Front. Neurosci., 2015, 9, 400.
[http://dx.doi.org/10.3389/fnins.2015.00400] [PMID: 26578862]
[193]
van Dis, V.; Kuijpers, M.; Haasdijk, E.D.; Teuling, E.; Oakes, S.A.; Hoogenraad, C.C.; Jaarsma, D. Golgi fragmentation precedes neuromuscular denervation and is associated with endosome abnormalities in SOD1-ALS mouse motor neurons. Acta Neuropathol. Commun., 2014, 2(1), 38.
[http://dx.doi.org/10.1186/2051-5960-2-38] [PMID: 24708899]
[194]
Sasaki, S.; Iwata, M. Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol., 2007, 66(1), 10-16.
[http://dx.doi.org/10.1097/nen.0b013e31802c396b] [PMID: 17204932]
[195]
Singh, T.; Jiao, Y.; Ferrando, L.M.; Yablonska, S.; Li, F.; Horoszko, E.C.; Lacomis, D.; Friedlander, R.M.; Carlisle, D.L. Neuronal mitochondrial dysfunction in sporadic amyotrophic lateral sclerosis is developmentally regulated. Sci. Rep., 2021, 11(1), 18916.
[http://dx.doi.org/10.1038/s41598-021-97928-7] [PMID: 34556702]
[196]
Thau, N.; Knippenberg, S.; Körner, S.; Rath, K.J.; Dengler, R.; Petri, S. Decreased mRNA expression of PGC-1α and PGC-1α-regulated factors in the SOD1G93A ALS mouse model and in human sporadic ALS. J. Neuropathol. Exp. Neurol., 2012, 71(12), 1064-1074.
[http://dx.doi.org/10.1097/NEN.0b013e318275df4b] [PMID: 23147503]
[197]
Moller, A.; Bauer, C.S.; Cohen, R.N.; Webster, C.P.; De Vos, K.J. Amyotrophic lateral sclerosis-associated mutant SOD1 inhibits anterograde axonal transport of mitochondria by reducing Miro1 levels. Hum. Mol. Genet., 2017, 26(23), 4668-4679.
[http://dx.doi.org/10.1093/hmg/ddx348] [PMID: 28973175]
[198]
Davis, S.A.; Itaman, S.; Khalid-Janney, C.M.; Sherard, J.A.; Dowell, J.A.; Cairns, N.J.; Gitcho, M.A. TDP-43 interacts with mitochondrial proteins critical for mitophagy and mitochondrial dynamics. Neurosci. Lett., 2018, 678, 8-15.
[http://dx.doi.org/10.1016/j.neulet.2018.04.053] [PMID: 29715546]
[199]
Chen, J.; Bassot, A.; Giuliani, F.; Simmen, T. Amyotrophic lateral sclerosis (ALS): Stressed by dysfunctional mitochondria-endoplasmic reticulum contacts (MERCs). Cells, 2021, 10(7), 1789.
[http://dx.doi.org/10.3390/cells10071789] [PMID: 34359958]
[200]
Wang, T.; Liu, H.; Itoh, K.; Oh, S.; Zhao, L.; Murata, D.; Sesaki, H.; Hartung, T.; Na, C.H.; Wang, J. C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly. Cell Metab., 2021, 33(3), 531-546.e9.
[http://dx.doi.org/10.1016/j.cmet.2021.01.005] [PMID: 33545050]
[201]
Obrador, E.; Salvador, R.; López-Blanch, R.; Jihad-Jebbar, A.; Vallés, S.L.; Estrela, J.M. Oxidative stress, neuroinflammation and mitochondria in the pathophysiology of amyotrophic lateral sclerosis. Antioxidants, 2020, 9(9), 901.
[http://dx.doi.org/10.3390/antiox9090901] [PMID: 32971909]
[202]
Smith, E.F.; Shaw, P.J.; De Vos, K.J. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci. Lett., 2019, 710, 132933.
[http://dx.doi.org/10.1016/j.neulet.2017.06.052] [PMID: 28669745]
[203]
Kazama, M.; Kato, Y.; Kakita, A.; Noguchi, N.; Urano, Y.; Masui, K.; Niida-Kawaguchi, M.; Yamamoto, T.; Watabe, K.; Kitagawa, K.; Shibata, N. Astrocytes release glutamate via cystine/glutamate antiporter upregulated in response to increased oxidative stress related to sporadic amyotrophic lateral sclerosis. Neuropathology, 2020, 40(6), 587-598.
[http://dx.doi.org/10.1111/neup.12716] [PMID: 33305472]
[204]
Pollari, E.; Goldsteins, G.; Bart, G.; Koistinaho, J.; Giniatullin, R. The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis. Front. Cell. Neurosci., 2014, 8, 131.
[http://dx.doi.org/10.3389/fncel.2014.00131] [PMID: 24860432]
[205]
Tsang, C.K.; Liu, Y.; Thomas, J.; Zhang, Y.; Zheng, X.F.S. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat. Commun., 2014, 5(1), 3446.
[http://dx.doi.org/10.1038/ncomms4446] [PMID: 24647101]
[206]
Goh, C.W.; Lee, I.C.; Sundaram, J.R.; George, S.E.; Yusoff, P.; Brush, M.H.; Sze, N.S.K.; Shenolikar, S. Chronic oxidative stress promotes GADD34-mediated phosphorylation of the TAR DNA-binding protein TDP-43, a modification linked to neurodegeneration. J. Biol. Chem., 2018, 293(1), 163-176.
[http://dx.doi.org/10.1074/jbc.M117.814111] [PMID: 29109149]
[207]
Jagaraj, C.J.; Parakh, S.; Atkin, J.D. Emerging evidence highlighting the importance of redox dysregulation in the pathogenesis of amyotrophic lateral sclerosis (ALS). Front. Cell. Neurosci., 2021, 14, 581950.
[http://dx.doi.org/10.3389/fncel.2020.581950] [PMID: 33679322]
[208]
Zala, D.; Hinckelmann, M.V.; Yu, H.; Lyra da Cunha, M.M.; Liot, G.; Cordelières, F.P.; Marco, S.; Saudou, F. Vesicular glycolysis provides on-board energy for fast axonal transport. Cell, 2013, 152(3), 479-491.
[http://dx.doi.org/10.1016/j.cell.2012.12.029] [PMID: 23374344]
[209]
Wang, T.; Tian, X.; Kim, H.B.; Jang, Y.; Huang, Z.; Na, C.H.; Wang, J. Intracellular energy controls dynamics of stress-induced ribonucleoprotein granules. Nat. Commun., 2022, 13(1), 5584.
[http://dx.doi.org/10.1038/s41467-022-33079-1] [PMID: 36151083]
[210]
Rodriguez-Rodriguez, P.; Fernandez, E.; Almeida, A.; Bolaños, J.P. Excitotoxic stimulus stabilizes PFKFB3 causing pentose-phosphate pathway to glycolysis switch and neurodegeneration. Cell Death Differ., 2012, 19(10), 1582-1589.
[http://dx.doi.org/10.1038/cdd.2012.33] [PMID: 22421967]
[211]
Vandoorne, T.; De Bock, K.; Van Den Bosch, L. Energy metabolism in ALS: an underappreciated opportunity? Acta Neuropathol., 2018, 135(4), 489-509.
[http://dx.doi.org/10.1007/s00401-018-1835-x] [PMID: 29549424]
[212]
Pennetta, G.; Welte, M.A. Emerging links between lipid droplets and motor neuron diseases. Dev. Cell, 2018, 45(4), 427-432.
[http://dx.doi.org/10.1016/j.devcel.2018.05.002] [PMID: 29787708]
[213]
Cistaro, A.; Pagani, M.; Montuschi, A.; Calvo, A.; Moglia, C.; Canosa, A.; Restagno, G.; Brunetti, M.; Traynor, B.J.; Nobili, F.; Carrara, G.; Fania, P.; Lopiano, L.; Valentini, M.C.; Chiò, A. The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients. Eur. J. Nucl. Med. Mol. Imaging, 2014, 41(5), 844-852.
[http://dx.doi.org/10.1007/s00259-013-2667-5] [PMID: 24445987]
[214]
Marini, C.; Morbelli, S.; Cistaro, A.; Campi, C.; Caponnetto, C.; Bauckneht, M.; Bellini, A.; Buschiazzo, A.; Calamia, I.; Beltrametti, M.C.; Margotti, S.; Fania, P.; Poggi, I.; Cabona, C.; Capitanio, S.; Piva, R.; Calvo, A.; Moglia, C.; Canosa, A.; Massone, A.; Nobili, F.; Mancardi, G.; Chiò, A.; Piana, M.; Sambuceti, G. Interplay between spinal cord and cerebral cortex metabolism in amyotrophic lateral sclerosis. Brain, 2018, 141(8), 2272-2279.
[http://dx.doi.org/10.1093/brain/awy152] [PMID: 30730551]
[215]
Bauckneht, M.; Lai, R.; Miceli, A.; Schenone, D.; Cossu, V.; Donegani, M.I.; Raffa, S.; Borra, A.; Marra, S.; Campi, C.; Orengo, A.; Massone, A.M.; Tagliafico, A.; Caponnetto, C.; Cabona, C.; Cistaro, A.; Chiò, A.; Morbelli, S.; Nobili, F.; Sambuceti, G.; Piana, M.; Marini, C. Spinal cord hypermetabolism extends to skeletal muscle in amyotrophic lateral sclerosis: a computational approach to [18F]-fluorodeoxyglucose PET/CT images. EJNMMI Res., 2020, 10(1), 23.
[http://dx.doi.org/10.1186/s13550-020-0607-5] [PMID: 32201914]
[216]
Miyazaki, K.; Masamoto, K.; Morimoto, N.; Kurata, T.; Mimoto, T.; Obata, T.; Kanno, I.; Abe, K. Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice. J. Cereb. Blood Flow Metab., 2012, 32(3), 456-467.
[http://dx.doi.org/10.1038/jcbfm.2011.155] [PMID: 22068226]
[217]
Dodge, J.C.; Treleaven, C.M.; Fidler, J.A.; Tamsett, T.J.; Bao, C.; Searles, M.; Taksir, T.V.; Misra, K.; Sidman, R.L.; Cheng, S.H.; Shihabuddin, L.S. Metabolic signatures of amyotrophic lateral sclerosis reveal insights into disease pathogenesis. Proc. Natl. Acad. Sci. USA, 2013, 110(26), 10812-10817.
[http://dx.doi.org/10.1073/pnas.1308421110] [PMID: 23754387]
[218]
Tefera, T.W.; Steyn, F.J.; Ngo, S.T.; Borges, K. CNS glucose metabolism in Amyotrophic Lateral Sclerosis: a therapeutic target? Cell Biosci., 2021, 11(1), 14.
[http://dx.doi.org/10.1186/s13578-020-00511-2] [PMID: 33431046]
[219]
Steyn, F.J.; Li, R.; Kirk, S.E.; Tefera, T.W.; Xie, T.Y.; Tracey, T.J.; Kelk, D.; Wimberger, E.; Garton, F.C.; Roberts, L.; Chapman, S.E.; Coombes, J.S.; Leevy, W.M.; Ferri, A.; Valle, C.; René, F.; Loeffler, J.P.; McCombe, P.A.; Henderson, R.D.; Ngo, S.T. Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis. Brain Commun., 2020, 2(2), fcaa154.
[http://dx.doi.org/10.1093/braincomms/fcaa154] [PMID: 33241210]
[220]
Tefera, T.W.; Borges, K. Neuronal glucose metabolism is impaired while astrocytic TCA cycling is unaffected at symptomatic stages in the hSOD1 G93A mouse model of amyotrophic lateral sclerosis. J. Cereb. Blood Flow Metab., 2019, 39(9), 1710-1724.
[http://dx.doi.org/10.1177/0271678X18764775] [PMID: 29553298]
[221]
Lee, H.; Lee, J.J.; Park, N.Y.; Dubey, S.K.; Kim, T.; Ruan, K.; Lim, S.B.; Park, S.H.; Ha, S.; Kovlyagina, I.; Kim, K.; Kim, S.; Oh, Y.; Kim, H.; Kang, S.U.; Song, M.R.; Lloyd, T.E.; Maragakis, N.J.; Hong, Y.B.; Eoh, H.; Lee, G. Multi-omic analysis of selectively vulnerable motor neuron subtypes implicates altered lipid metabolism in ALS. Nat. Neurosci., 2021, 24(12), 1673-1685.
[http://dx.doi.org/10.1038/s41593-021-00944-z] [PMID: 34782793]
[222]
Palamiuc, L.; Schlagowski, A.; Ngo, S.T.; Vernay, A.; Dirrig-Grosch, S.; Henriques, A.; Boutillier, A.L.; Zoll, J.; Echaniz-Laguna, A.; Loeffler, J.P.; René, F. A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis. EMBO Mol. Med., 2015, 7(5), 526-546.
[http://dx.doi.org/10.15252/emmm.201404433] [PMID: 25820275]
[223]
Yudkoff, M.; Daikhin, Y.; Horyn, O.; Nissim, I.; Nissim, I. Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia, 2008, 49(Suppl. 8), 73-75.
[http://dx.doi.org/10.1111/j.1528-1167.2008.01841.x] [PMID: 19049594]
[224]
Scaricamazza, S.; Salvatori, I.; Giacovazzo, G.; Loeffler, J.P.; Renè, F.; Rosina, M.; Quessada, C.; Proietti, D.; Heil, C.; Rossi, S.; Battistini, S.; Giannini, F.; Volpi, N.; Steyn, F.J.; Ngo, S.T.; Ferraro, E.; Madaro, L.; Coccurello, R.; Valle, C.; Ferri, A. Skeletal-muscle metabolic reprogramming in ALS-SOD1G93A mice predates disease onset and is a promising therapeutic target. iScience, 2020, 23(5), 101087.
[http://dx.doi.org/10.1016/j.isci.2020.101087] [PMID: 32371370]
[225]
Szelechowski, M.; Amoedo, N.; Obre, E.; Léger, C.; Allard, L.; Bonneu, M.; Claverol, S.; Lacombe, D.; Oliet, S.; Chevallier, S.; Le Masson, G.; Rossignol, R. Metabolic reprogramming in amyotrophic lateral sclerosis. Sci. Rep., 2018, 8(1), 3953.
[http://dx.doi.org/10.1038/s41598-018-22318-5] [PMID: 29500423]
[226]
Dodge, J.C.; Jensen, E.H.; Yu, J.; Sardi, S.P.; Bialas, A.R.; Taksir, T.V.; Bangari, D.S.; Shihabuddin, L.S. Neutral lipid cacostasis contributes to disease pathogenesis in amyotrophic lateral sclerosis. J. Neurosci., 2020, 40(47), 9137-9147.
[http://dx.doi.org/10.1523/JNEUROSCI.1388-20.2020] [PMID: 33051352]
[227]
Henriques, A.; Huebecker, M.; Blasco, H.; Keime, C.; Andres, C.R.; Corcia, P.; Priestman, D.A.; Platt, F.M.; Spedding, M.; Loeffler, J.P. Inhibition of β-Glucocerebrosidase activity preserves motor unit integrity in a mouse model of amyotrophic lateral sclerosis. Sci. Rep., 2017, 7(1), 5235.
[http://dx.doi.org/10.1038/s41598-017-05313-0] [PMID: 28701774]
[228]
Sipione, S.; Monyror, J.; Galleguillos, D.; Steinberg, N.; Kadam, V. Gangliosides in the brain: Physiology, pathophysiology and therapeutic applications. Front. Neurosci., 2020, 14, 572965.
[http://dx.doi.org/10.3389/fnins.2020.572965] [PMID: 33117120]
[229]
Tracey, T.J.; Steyn, F.J.; Wolvetang, E.J.; Ngo, S.T. Neuronal lipid metabolism: multiple pathways driving functional outcomes in health and disease. Front. Mol. Neurosci., 2018, 11, 10.
[http://dx.doi.org/10.3389/fnmol.2018.00010] [PMID: 29410613]
[230]
Schmitt, F.; Hussain, G.; Dupuis, L.; Loeffler, J.P.; Henriques, A. A plural role for lipids in motor neuron diseases: Energy, signaling and structure. Front. Cell. Neurosci., 2014, 8, 25.
[http://dx.doi.org/10.3389/fncel.2014.00025] [PMID: 24600344]
[231]
Mouzat, K.; Molinari, N.; Kantar, J.; Polge, A.; Corcia, P.; Couratier, P.; Clavelou, P.; Juntas-Morales, R.; Pageot, N.; Lobaccaro, J.M.A.; Raoul, C.; Lumbroso, S.; Camu, W. Liver X receptor genes variants modulate ALS phenotype. Mol. Neurobiol., 2018, 55(3), 1959-1965.
[http://dx.doi.org/10.1007/s12035-017-0453-2] [PMID: 28244008]
[232]
Wills, A.M.; Hubbard, J.; Macklin, E.A.; Glass, J.; Tandan, R.; Simpson, E.P.; Brooks, B.; Gelinas, D.; Mitsumoto, H.; Mozaffar, T.; Hanes, G.P.; Ladha, S.S.; Heiman-Patterson, T.; Katz, J.; Lou, J.S.; Mahoney, K.; Grasso, D.; Lawson, R.; Yu, H.; Cudkowicz, M. Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet, 2014, 383(9934), 2065-2072.
[http://dx.doi.org/10.1016/S0140-6736(14)60222-1] [PMID: 24582471]
[233]
Fang, F.; Ingre, C.; Roos, P.; Kamel, F.; Piehl, F. Risk factors for amyotrophic lateral sclerosis. Clin. Epidemiol., 2015, 7, 181-193.
[http://dx.doi.org/10.2147/CLEP.S37505] [PMID: 25709501]
[234]
Goutman, S.A.; Feldman, E.L. Voicing the Need for Amyotrophic Lateral Sclerosis Environmental Research. JAMA Neurol., 2020, 77(5), 543-544.
[http://dx.doi.org/10.1001/jamaneurol.2020.0051] [PMID: 32119032]
[235]
Allis, C.D.; Jenuwein, T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet., 2016, 17(8), 487-500.
[http://dx.doi.org/10.1038/nrg.2016.59] [PMID: 27346641]
[236]
Worpenberg, L.; Paolantoni, C.; Roignant, J-Y. Functional interplay within the epitranscriptome: Reality or fiction? BioEssays, 2021, e2100174.
[http://dx.doi.org/10.1002/bies.202100174] [PMID: 34873719]
[237]
Appleby-Mallinder, C.; Schaber, E.; Kirby, J.; Shaw, P.J.; Cooper-Knock, J.; Heath, P.R.; Highley, J.R. TDP43 proteinopathy is associated with aberrant DNA methylation in human amyotrophic lateral sclerosis. Neuropathol. Appl. Neurobiol., 2021, 47(1), 61-72.
[http://dx.doi.org/10.1111/nan.12625] [PMID: 32365404]
[238]
Ozyurt, T.; Gautam, M. Differential epigenetic signature of corticospinal motor neurons in ALS. Brain Sci., 2021, 11(6), 754.
[http://dx.doi.org/10.3390/brainsci11060754] [PMID: 34200232]
[239]
Xi, Z.; Zhang, M.; Bruni, A.C.; Maletta, R.G.; Colao, R.; Fratta, P.; Polke, J.M.; Sweeney, M.G.; Mudanohwo, E.; Nacmias, B.; Sorbi, S.; Tartaglia, M.C.; Rainero, I.; Rubino, E.; Pinessi, L.; Galimberti, D.; Surace, E.I.; McGoldrick, P.; McKeever, P.; Moreno, D.; Sato, C.; Liang, Y.; Keith, J.; Zinman, L.; Robertson, J.; Rogaeva, E. The C9orf72 repeat expansion itself is methylated in ALS and FTLD patients. Acta Neuropathol., 2015, 129(5), 715-727.
[http://dx.doi.org/10.1007/s00401-015-1401-8] [PMID: 25716178]
[240]
Wong, M.; Gertz, B.; Chestnut, B.A.; Martin, L.J. Mitochondrial DNMT3A and DNA methylation in skeletal muscle and CNS of transgenic mouse models of ALS. Front. Cell. Neurosci., 2013, 7, 279.
[http://dx.doi.org/10.3389/fncel.2013.00279] [PMID: 24399935]
[241]
Simpson, C.L.; Lemmens, R.; Miskiewicz, K.; Broom, W.J.; Hansen, V.K.; van Vught, P.W.J.; Landers, J.E.; Sapp, P.; Van Den Bosch, L.; Knight, J.; Neale, B.M.; Turner, M.R.; Veldink, J.H.; Ophoff, R.A.; Tripathi, V.B.; Beleza, A.; Shah, M.N.; Proitsi, P.; Van Hoecke, A.; Carmeliet, P.; Horvitz, H.R.; Leigh, P.N.; Shaw, C.E.; van den Berg, L.H.; Sham, P.C.; Powell, J.F.; Verstreken, P.; Brown, R.H., Jr; Robberecht, W.; Al-Chalabi, A. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. Hum. Mol. Genet., 2009, 18(3), 472-481.
[http://dx.doi.org/10.1093/hmg/ddn375] [PMID: 18996918]
[242]
Taes, I.; Timmers, M.; Hersmus, N.; Bento-Abreu, A.; Van Den Bosch, L.; Van Damme, P.; Auwerx, J.; Robberecht, W. Hdac6 deletion delays disease progression in the SOD1G93A mouse model of ALS. Hum. Mol. Genet., 2013, 22(9), 1783-1790.
[http://dx.doi.org/10.1093/hmg/ddt028] [PMID: 23364049]
[243]
Chen, S.; Zhang, X.J.; Li, L.X.; Wang, Y.; Zhong, R.J.; Le, W. Histone deacetylase 6 delays motor neuron degeneration by ameliorating the autophagic flux defect in a transgenic mouse model of amyotrophic lateral sclerosis. Neurosci. Bull., 2015, 31(4), 459-468.
[http://dx.doi.org/10.1007/s12264-015-1539-3] [PMID: 26164555]
[244]
Pigna, E.; Simonazzi, E.; Sanna, K.; Bernadzki, K.M.; Proszynski, T.; Heil, C.; Palacios, D.; Adamo, S.; Moresi, V. Histone deacetylase 4 protects from denervation and skeletal muscle atrophy in a murine model of amyotrophic lateral sclerosis. EBioMedicine, 2019, 40, 717-732.
[http://dx.doi.org/10.1016/j.ebiom.2019.01.038] [PMID: 30713114]
[245]
Tibshirani, M.; Tradewell, M.L.; Mattina, K.R.; Minotti, S.; Yang, W.; Zhou, H.; Strong, M.J.; Hayward, L.J.; Durham, H.D. Cytoplasmic sequestration of FUS/TLS associated with ALS alters histone marks through loss of nuclear protein arginine methyltransferase 1. Hum. Mol. Genet., 2015, 24(3), 773-786.
[http://dx.doi.org/10.1093/hmg/ddu494] [PMID: 25274782]
[246]
Masala, A.; Sanna, S.; Esposito, S.; Rassu, M.; Galioto, M.; Zinellu, A.; Carru, C.; Carrì, M.T.; Iaccarino, C.; Crosio, C. Epigenetic changes associated with the expression of amyotrophic lateral sclerosis (ALS) causing genes. Neuroscience, 2018, 390, 1-11.
[http://dx.doi.org/10.1016/j.neuroscience.2018.08.009] [PMID: 30134203]
[247]
Vijayakumar, U.G.; Milla, V.; Cynthia Stafford, M.Y.; Bjourson, A.J.; Duddy, W.; Duguez, S.M.R. A systematic review of suggested molecular strata, biomarkers and their tissue sources in ALS. Front. Neurol., 2019, 10, 400.
[http://dx.doi.org/10.3389/fneur.2019.00400] [PMID: 31139131]
[248]
Foggin, S.; Mesquita-Ribeiro, R.; Dajas-Bailador, F.; Layfield, R. Biological significance of microRNA biomarkers in ALS-innocent bystanders or disease culprits? Front. Neurol., 2019, 10, 578.
[http://dx.doi.org/10.3389/fneur.2019.00578] [PMID: 31244752]
[249]
Ravnik-Glavač, M.; Glavač, D. Circulating RNAs as potential Biomarkers in amyotrophic lateral sclerosis. Int. J. Mol. Sci., 2020, 21(5), 1714.
[http://dx.doi.org/10.3390/ijms21051714] [PMID: 32138249]
[250]
Angelova, M.T.; Dimitrova, D.G.; Dinges, N.; Lence, T.; Worpenberg, L.; Carré, C.; Roignant, J.Y. The emerging field of epitranscriptomics in neurodevelopmental and neuronal disorders. Front. Bioeng. Biotechnol., 2018, 6, 46.
[http://dx.doi.org/10.3389/fbioe.2018.00046] [PMID: 29707539]
[251]
Hosaka, T.; Tsuji, H.; Tamaoka, A. Biomolecular modifications linked to oxidative stress in amyotrophic lateral sclerosis: determining promising biomarkers related to oxidative stress. Processes (Basel), 2021, 9(9), 1667.
[http://dx.doi.org/10.3390/pr9091667]
[252]
Hideyama, T.; Yamashita, T.; Aizawa, H.; Tsuji, S.; Kakita, A.; Takahashi, H.; Kwak, S. Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons. Neurobiol. Dis., 2012, 45(3), 1121-1128.
[http://dx.doi.org/10.1016/j.nbd.2011.12.033] [PMID: 22226999]
[253]
Sasaki, S.; Yamashita, T.; Shin, K. Autophagy in spinal motor neurons of conditional ADAR2-knockout mice: An implication for a role of calcium in increased autophagy flux in ALS. Neurosci. Lett., 2015, 598, 79-84.
[http://dx.doi.org/10.1016/j.neulet.2015.05.025] [PMID: 25980994]
[254]
Moore, S.; Alsop, E.; Lorenzini, I.; Starr, A.; Rabichow, B.E.; Mendez, E.; Levy, J.L.; Burciu, C.; Reiman, R.; Chew, J.; Belzil, V.V.; W. Dickson, D. Robertson, J.; Staats, K.A.; Ichida, J.K.; Petrucelli, L.; Van Keuren-Jensen, K.; Sattler, R. ADAR2 mislocalization and widespread RNA editing aberrations in C9orf72-mediated ALS/FTD. Acta Neuropathol., 2019, 138(1), 49-65.
[http://dx.doi.org/10.1007/s00401-019-01999-w] [PMID: 30945056]
[255]
Quoibion, A. m6A RNA Methylation and TARDBP, a Gene Implicated in Amyotrophic Lateral Sclerosis. McGill University: Montréal, 2017. Thesis.
[256]
Kim, H.J.; Kim, N.C.; Wang, Y.D.; Scarborough, E.A.; Moore, J.; Diaz, Z.; MacLea, K.S.; Freibaum, B.; Li, S.; Molliex, A.; Kanagaraj, A.P.; Carter, R.; Boylan, K.B.; Wojtas, A.M.; Rademakers, R.; Pinkus, J.L.; Greenberg, S.A.; Trojanowski, J.Q.; Traynor, B.J.; Smith, B.N.; Topp, S.; Gkazi, A.S.; Miller, J.; Shaw, C.E.; Kottlors, M.; Kirschner, J.; Pestronk, A.; Li, Y.R.; Ford, A.F.; Gitler, A.D.; Benatar, M.; King, O.D.; Kimonis, V.E.; Ross, E.D.; Weihl, C.C.; Shorter, J.; Taylor, J.P. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature, 2013, 495(7442), 467-473.
[http://dx.doi.org/10.1038/nature11922] [PMID: 23455423]
[257]
Mitropoulos, K.; Merkouri, P.E.; Xiromerisiou, G.; Balasopoulou, A.; Charalampidou, K.; Galani, V.; Zafeiri, K.V.; Dardiotis, E.; Ralli, S.; Deretzi, G.; John, A.; Kydonopoulou, K.; Papadopoulou, E.; di Pardo, A.; Akcimen, F.; Loizedda, A.; Dobričić, V.; Novaković, I.; Kostić, V.S.; Mizzi, C.; Peters, B.A.; Basak, N.; Orrù, S.; Kiskinis, E.; Cooper, D.N.; Gerou, S.; Drmanac, R.; Bartsakoulia, M.; Tsermpini, E.E.; Hadjigeorgiou, G.M.; Ali, B.R.; Katsila, T.; Patrinos, G.P. Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients. Hum. Genomics, 2017, 11(1), 30.
[http://dx.doi.org/10.1186/s40246-017-0126-2] [PMID: 29216901]
[258]
Blanco, S.; Dietmann, S.; Flores, J.V.; Hussain, S.; Kutter, C.; Humphreys, P.; Lukk, M.; Lombard, P.; Treps, L.; Popis, M.; Kellner, S.; Hölter, S.M.; Garrett, L.; Wurst, W.; Becker, L.; Klopstock, T.; Fuchs, H.; Gailus-Durner, V.; Hrabĕ de Angelis, M.; Káradóttir, R.T.; Helm, M.; Ule, J.; Gleeson, J.G.; Odom, D.T.; Frye, M. Aberrant methylation of t RNA s links cellular stress to neuro‐developmental disorders. EMBO J., 2014, 33(18), 2020-2039.
[http://dx.doi.org/10.15252/embj.201489282] [PMID: 25063673]
[259]
Hartung, T.; Rhein, M.; Kalmbach, N.; Thau-Habermann, N.; Naujock, M.; Müschen, L.; Frieling, H.; Sterneckert, J.; Hermann, A.; Wegner, F.; Petri, S. Methylation and expression of mutant FUS in motor neurons differentiated from induced pluripotent stem cells from ALS patients. Front. Cell Dev. Biol., 2021, 9, 774751.
[http://dx.doi.org/10.3389/fcell.2021.774751] [PMID: 34869374]
[260]
Hogg, M.C.; Rayner, M.; Susdalzew, S.; Monsefi, N.; Crivello, M.; Woods, I.; Resler, A.; Blackbourn, L.; Fabbrizio, P.; Trolese, M.C.; Nardo, G.; Bendotti, C.; van den Berg, L.H.; van Es, M.A.; Prehn, J.H.M. 5′ValCAC tRNA fragment generated as part of a protective angiogenin response provides prognostic value in amyotrophic lateral sclerosis. Brain Commun., 2020, 2(2), fcaa138.
[http://dx.doi.org/10.1093/braincomms/fcaa138] [PMID: 33543130]
[261]
Taylor, R.; Hamid, F.; Fielding, T.; Gordon, P.M.; Maloney, M.; Makeyev, E.V.; Houart, C. Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS. Nat. Commun., 2022, 13(1), 6994.
[http://dx.doi.org/10.1038/s41467-022-34331-4] [PMID: 36414621]
[262]
Mead, R.J.; Shan, N.; Reiser, H.J.; Marshall, F.; Shaw, P.J. Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nat. Rev. Drug Discov., 2023, 22(3), 185-212.
[http://dx.doi.org/10.1038/s41573-022-00612-2] [PMID: 36543887]
[263]
Corcia, P.; Beltran, S.; Bakkouche, S.E.; Couratier, P. Therapeutic news in ALS. Rev. Neurol., 2021, 177(5), 544-549.
[http://dx.doi.org/10.1016/j.neurol.2020.12.003]
[264]
Ketabforoush, A.H.M.E.; Chegini, R.; Barati, S.; Tahmasebi, F.; Moghisseh, B.; Joghataei, M.T.; Faghihi, F.; Azedi, F. Masitinib: The promising actor in the next season of the amyotrophic lateral sclerosis treatment series. Biomed. Pharmacother., 2023, 160, 114378.
[http://dx.doi.org/10.1016/j.biopha.2023.114378] [PMID: 36774721]
[265]
Eisen, A.; Kim, S.; Pant, B. Amyotrophic lateral sclerosis (ALS): A phylogenetic disease of the corticomotoneuron? Muscle Nerve, 1992, 15(2), 219-224.
[http://dx.doi.org/10.1002/mus.880150215] [PMID: 1549143]
[266]
Marques, C.; Burg, T.; Scekic-Zahirovic, J.; Fischer, M.; Rouaux, C. Upper and lower motor neuron degenerations are somatotopically related and temporally ordered in the Sod1 mouse model of amyotrophic lateral sclerosis. Brain Sci., 2021, 11(3), 369.
[http://dx.doi.org/10.3390/brainsci11030369] [PMID: 33805792]
[267]
Lu, S.; Hu, J.; Arogundade, O.A.; Goginashvili, A.; Vazquez-Sanchez, S.; Diedrich, J.K.; Gu, J.; Blum, J.; Oung, S.; Ye, Q.; Yu, H.; Ravits, J.; Liu, C.; Yates, J.R., III; Cleveland, D.W. Heat-shock chaperone HSPB1 regulates cytoplasmic TDP-43 phase separation and liquid-to-gel transition. Nat. Cell Biol., 2022, 24(9), 1378-1393.
[http://dx.doi.org/10.1038/s41556-022-00988-8] [PMID: 36075972]
[268]
Pradhan, J.; Noakes, P.G.; Bellingham, M.C. The role of altered BDNF/TrkB signaling in amyotrophic lateral sclerosis. Front. Cell. Neurosci., 2019, 13, 368.
[http://dx.doi.org/10.3389/fncel.2019.00368] [PMID: 31456666]
[269]
Paganoni, S.; Berry, J.D.; Quintana, M.; Macklin, E.; Saville, B.R.; Detry, M.A.; Chase, M.; Sherman, A.V.; Yu, H.; Drake, K.; Andrews, J.; Shefner, J.; Chibnik, L.B.; Vestrucci, M.; Cudkowicz, M.E. Adaptive platform trials to transform amyotrophic lateral sclerosis therapy development. Ann. Neurol., 2022, 91(2), 165-175.
[http://dx.doi.org/10.1002/ana.26285] [PMID: 34935174]
[270]
Jacquez, G.M.; Sabel, C.E.; Shi, C. Genetic GIScience: toward a place-based synthesis of the genome, exposome, and behavome. Ann. Assoc. Am. Geogr., 2015, 105(3), 454-472.
[http://dx.doi.org/10.1080/00045608.2015.1018777] [PMID: 26339073]
[271]
Fidler, J.A.; Treleaven, C.M.; Frakes, A.; Tamsett, T.J.; McCrate, M.; Cheng, S.H.; Shihabuddin, L.S.; Kaspar, B.K.; Dodge, J.C. Disease progression in a mouse model of amyotrophic lateral sclerosis: the influence of chronic stress and corticosterone. FASEB J., 2011, 25(12), 4369-4377.
[http://dx.doi.org/10.1096/fj.11-190819] [PMID: 21876068]
[272]
Calabrese, V.; Mancuso, C.; Calvani, M.; Rizzarelli, E.; Butterfield, D.A.; Giuffrida Stella, A.M. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat. Rev. Neurosci., 2007, 8(10), 766-775.
[http://dx.doi.org/10.1038/nrn2214] [PMID: 17882254]
[273]
Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; Calabrese, E.J.; Mattson, M.P. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid. Redox Signal., 2010, 13(11), 1763-1811.
[http://dx.doi.org/10.1089/ars.2009.3074] [PMID: 20446769]
[274]
Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; Calabrese, E.J. Vitagenes, cellular stress response, and acetylcarnitine: Relevance to hormesis. Biofactors, 2009, 35(2), 146-160.
[http://dx.doi.org/10.1002/biof.22] [PMID: 19449442]
[275]
Anzilotti, S.; Brancaccio, P.; Simeone, G.; Valsecchi, V.; Vinciguerra, A.; Secondo, A.; Petrozziello, T.; Guida, N.; Sirabella, R.; Cuomo, O.; Cepparulo, P.; Herchuelz, A.; Amoroso, S.; Di Renzo, G.; Annunziato, L.; Pignataro, G. Preconditioning, induced by sub-toxic dose of the neurotoxin L-BMAA, delays ALS progression in mice and prevents Na+/Ca2+ exchanger 3 downregulation. Cell Death Dis., 2018, 9(2), 206.
[http://dx.doi.org/10.1038/s41419-017-0227-9] [PMID: 29434186]
[276]
Siracusa, R.; Scuto, M.; Fusco, R.; Trovato, A.; Ontario, M.L.; Crea, R.; Di Paola, R.; Cuzzocrea, S.; Calabrese, V. Anti-inflammatory and anti-oxidant activity of Hidrox® in rotenone-induced Parkinson’s disease in mice. Antioxidants, 2020, 9(9), 824.
[http://dx.doi.org/10.3390/antiox9090824] [PMID: 32899274]
[277]
Kim, D.; Nguyen, M.D.; Dobbin, M.M.; Fischer, A.; Sananbenesi, F.; Rodgers, J.T.; Delalle, I.; Baur, J.A.; Sui, G.; Armour, S.M.; Puigserver, P.; Sinclair, D.A.; Tsai, L.H. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J., 2007, 26(13), 3169-3179.
[http://dx.doi.org/10.1038/sj.emboj.7601758] [PMID: 17581637]
[278]
Calabrese, E.J.; Calabrese, V.; Giordano, J. Brain health promotion: Tactics within a strategic approach based upon valid, yet evolving scientific evidence. Mech. Ageing Dev., 2022, 201, 111605.
[http://dx.doi.org/10.1016/j.mad.2021.111605] [PMID: 34798081]
[279]
Bauer, P.O. Methylation of C9orf72 expansion reduces RNA foci formation and dipeptide-repeat proteins expression in cells. Neurosci. Lett., 2016, 612, 204-209.
[http://dx.doi.org/10.1016/j.neulet.2015.12.018] [PMID: 26690922]
[280]
Lam, F.; Chu, J.; Choi, J.S.; Cao, C.; Hitchens, T.K.; Silverman, S.K. Epigenetic MRI: noninvasive imaging of DNA methylation in the brain. BioRxiv, 2021, 2021.08.20.457113.
[http://dx.doi.org/10.1101/2021.08.20.457113]
[281]
Choi, S.Y.; Lee, J.H.; Chung, A.Y.; Jo, Y.; Shin, J.; Park, H.C.; Kim, H.; Lopez-Gonzalez, R.; Ryu, J.R.; Sun, W. Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis. Cell Death Dis., 2020, 11(10), 888.
[http://dx.doi.org/10.1038/s41419-020-03102-8] [PMID: 33087694]
[282]
Paganoni, S.; Hendrix, S.; Dickson, S.P.; Knowlton, N.; Berry, J.D.; Elliott, M.A. Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: Long-term results from the Centaur trial. J Neurol. Neurosurg. Amp. Psychiatry, 2022, 93, 871.
[http://dx.doi.org/10.1136/jnnp-2022-329024]
[283]
Klingl, Y.E.; Pakravan, D.; Van Den, B.L. Opportunities for histone deacetylase inhibition in amyotrophic lateral sclerosis. Br. J. Pharmacol., 2020, 178(6), 1353-1372.
[http://dx.doi.org/10.1111/bph.15217]
[284]
Xia, Z.; Tang, M.; Ma, J.; Zhang, H.; Gimple, R.C.; Prager, B.C.; Tang, H.; Sun, C.; Liu, F.; Lin, P.; Mei, Y.; Du, R.; Rich, J.N.; Xie, Q. Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase. Nucleic Acids Res., 2021, 49(13), 7361-7374.
[http://dx.doi.org/10.1093/nar/gkab517] [PMID: 34181729]
[285]
Batra, R.; Nelles, D.A.; Pirie, E.; Blue, S.M.; Marina, R.J.; Wang, H.; Chaim, I.A.; Thomas, J.D.; Zhang, N.; Nguyen, V.; Aigner, S.; Markmiller, S.; Xia, G.; Corbett, K.D.; Swanson, M.S.; Yeo, G.W. Elimination of toxic microsatellite repeat expansion RNA by RNA-targeting Cas9. Cell, 2017, 170(5), 899-912.e10.
[http://dx.doi.org/10.1016/j.cell.2017.07.010] [PMID: 28803727]
[286]
Keogh, M.J.; Wei, W.; Aryaman, J.; Wilson, I.; Talbot, K.; Turner, M.R.; McKenzie, C.A.; Troakes, C.; Attems, J.; Smith, C.; Al Sarraj, S.; Morris, C.M.; Ansorge, O.; Pickering-Brown, S.; Jones, N.; Ironside, J.W.; Chinnery, P.F. Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains. J. Neurol. Neurosurg. Psychiatry, 2018, 89(8), 813-816.
[http://dx.doi.org/10.1136/jnnp-2017-317234] [PMID: 29332010]
[287]
Chiò, A.; Mazzini, L.; D’Alfonso, S.; Corrado, L.; Canosa, A.; Moglia, C.; Manera, U.; Bersano, E.; Brunetti, M.; Barberis, M.; Veldink, J.H.; van den Berg, L.H.; Pearce, N.; Sproviero, W.; McLaughlin, R.; Vajda, A.; Hardiman, O.; Rooney, J.; Mora, G.; Calvo, A.; Al-Chalabi, A. The multistep hypothesis of ALS revisited. Neurology, 2018, 91(7), e635-e642.
[http://dx.doi.org/10.1212/WNL.0000000000005996] [PMID: 30045958]

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