Abstract
Background & Objective: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that specifically affects motor neurons in the brain and in the spinal cord. Patients with amyotrophic lateral sclerosis usually die from respiratory failure within 3 to 5 years from when the symptoms first appear. Currently, there is no cure for amyotrophic lateral sclerosis. Accumulating evidence suggests that dismantling of neuromuscular junction is an early event in the pathogenesis of amyotrophic lateral sclerosis.
Conclusion: It is starting to realized that macrophage malfunction contributes to the disruption of neuromuscular junction. Modulation of macrophage activation states may stabilize neuromuscular junction and provide protection against motor neuron degeneration in amyotrophic lateral sclerosis.
Keywords: Amyotrophic lateral sclerosis, macrophage, inflammation, neuromuscular junction, peripheral nerve system, activation states.
Graphical Abstract
[1]
Ajroud-Driss S, Siddique T. Sporadic and hereditary amyotrophic lateral sclerosis (ALS). Biochim Biophys Acta 2015; 1852(4): 679-84.
[2]
Peters OM, Ghasemi M, Brown RH Jr. Emerging mechanisms of molecular pathology in ALS. J Clin Invest 2015; 125(6): 2548.
[3]
Chico L, Ienco EC, Bisordi C, et al. Amyotrophic lateral sclerosis and oxidative stress: A double-blind therapeutic trial after curcumin supplementation. CNS Neurol Disord Drug Targets 2018; 17(10): 767-79.
[4]
Chen H, Kankel MW, Su SC, Han SWS, Ofengeim D. Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD. Cell Death Differ 2018; 25(4): 646-60.
[5]
Mannucci C, Navarra M, Calapai F, et al. Neurological aspects of medical use of cannabidiol. CNS Neurol Disord Drug Targets 2017; 16(5): 541-53.
[6]
Caballero-Villarraso J, Galvan A, Escribano BM, Tunez I. Interrelationships among gut microbiota and host: paradigms, role in neurodegenerative diseases and future prospects. CNS Neurol Disord Drug Targets 2017; 16(8): 945-64.
[7]
Lino MM, Schneider C, Caroni P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J Neurosci 2002; 22(12): 4825-32.
[8]
Pramatarova A, Laganiere J, Roussel J, Brisebois K, Rouleau GA. Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J Neurosci 2001; 21(10): 3369-74.
[9]
Gong YH, Parsadanian AS, Andreeva A, Snider WD, Elliott JL. Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J Neurosci 2000; 20(2): 660-5.
[10]
Nagai M, Re DB, Nagata T, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 2007; 10(5): 615-22.
[11]
Beers DR, Henkel JS, Xiao Q, et al. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2006; 103(43): 16021-6.
[12]
Clement AM, Nguyen MD, Roberts EA, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 2003; 302(5642): 113-7.
[13]
Yamanaka K, Boillee S, Roberts EA, et al. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc Natl Acad Sci U S A 2008; 105(21): 7594-9.
[14]
Alexianu ME, Kozovska M, Appel SH. Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 2001; 57(7): 1282-9.
[15]
Barbeito AG, Mesci P, Boillee S. Motor neuron-immune interactions: the vicious circle of ALS. J Neural Transm 2010; 117(8): 981-1000.
[16]
Calvo A, Moglia C, Balma M, Chio A. Involvement of immune response in the pathogenesis of amyotrophic lateral sclerosis: a therapeutic opportunity? CNS Neurol Disord Drug Target 2010; 9(3): 325-30.
[17]
Troost D, van den Oord JJ, de Jong JM, Swaab DF. Lymphocytic infiltration in the spinal cord of patients with amyotrophic lateral sclerosis. Clin Neuropathol 1989; 8(6): 289-94.
[18]
Troost D, Van den Oord JJ, Vianney de Jong JM. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 1990; 16(5): 401-10.
[19]
Graves MC, Fiala M, Dinglasan LA, et al. Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells. Amyotroph Lateral Scler Motor Neuron Disord 2004; 5(4): 213-9.
[20]
Yiangou Y, Facer P, Durrenberger P, et al. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol 2006; 6: 12.
[21]
Zhang R, Gascon R, Miller RG, et al. MCP-1 chemokine receptor CCR2 is decreased on circulating monocytes in sporadic amyotrophic lateral sclerosis (sALS). J Neuroimmunol 2006; 179(1-2): 87-93.
[22]
Gowing G, Lalancette-Hebert M, Audet JN, Dequen F, Julien JP. Macrophage colony stimulating factor (M-CSF) exacerbates ALS disease in a mouse model through altered responses of microglia expressing mutant superoxide dismutase. Exp Neurol 2009; 220(2): 267-75.
[23]
Henkel JS, Engelhardt JI, Siklos L, et al. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol 2004; 55(2): 221-35.
[24]
Kuhle J, Lindberg RL, Regeniter A, et al. Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur J Neurol 2009; 16(6): 771-4.
[25]
Garbuzova-Davis S, Saporta S, Haller E, et al. Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS. PLoS One 2007; 2(11)e1205
[26]
Liu J, Wang F. Role of neuroinflammation in amyotrophic lateral sclerosis: cellular mechanisms and therapeutic implications. Front Immunol 2017; 8: 1005.
[27]
Yamasaki R, Tanaka M, Fukunaga M, et al. Restoration of microglial function by granulocyte-colony stimulating factor in ALS model mice. J Neuroimmunol 2010; 229(1-2): 51-62.
[28]
Gowing G, Philips T, Van Wijmeersch B, Audet JN, et al. Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase. J Neurosci 2008; 28(41): 10234-44.
[29]
Honma Y, Komori T, Kato S, Suda N, Kawata A, Oda M. An autopsy case of sporadic amyotrophic lateral sclerosis with 16-year survival without artificial ventilation. Neuropathology 1999; 19(1): 85-92.
[30]
O’Rourke JG, Bogdanik L, Yanez A, et al. C9orf72 is required for proper macrophage and microglial function in mice. Science 2016; 351(6279): 1324-9.
[31]
Swarup V, Phaneuf D, Dupre N, et al. Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kappaB-mediated pathogenic pathways. J Exp Med 2011; 208(12): 2429-47.
[32]
Correia AS, Patel P, Dutta K, Julien JP. Inflammation induces tdp-43 mislocalization and aggregation. PLoS One 2015; 10(10)e0140248
[33]
Sugiyama M, Takao M, Hatsuta H, et al. Increased number of astrocytes and macrophages/microglial cells in the corpus callosum in amyotrophic lateral sclerosis. Neuropathology 2013; 33(6): 591-9.
[34]
Hovden H, Frederiksen JL, Pedersen SW. Immune system alterations in amyotrophic lateral sclerosis. Acta Neurol Scand 2013; 128(5): 287-96.
[35]
Koval ED, Shaner C, Zhang P, et al. Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice. Hum Mol Genet 2013; 22(20): 4127-35.
[36]
Mizwicki MT, Fiala M, Magpantay L, et al. Tocilizumab attenuates inflammation in ALS patients through inhibition of IL6 receptor signaling. Am J Neurodegener Dis 2012; 1(3): 305-15.
[37]
Banati RB, Gehrmann J, Kellner M, Holsboer F. Antibodies against microglia/brain macrophages in the cerebrospinal fluid of a patient with acute amyotrophic lateral sclerosis and presenile dementia. Clin Neuropathol 1995; 14(4): 197-200.
[38]
Peviani M, Salvaneschi E, Bontempi L, et al. Neuroprotective effects of the Sigma-1 receptor (S1R) agonist PRE-084, in a mouse model of motor neuron disease not linked to SOD1 mutation. Neurobiol Dis 2014; 62: 218-32.
[39]
Rizzo F, Riboldi G, Salani S, et al. Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis. Cell Mol Life Sci 2014; 71(6): 999-1015.
[40]
Fischer LR, Culver DG, Tennant P, et al. Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 2004; 185(2): 232-40.
[41]
Dadon-Nachum M, Melamed E, Offen D. The “dying-back” phenomenon of motor neurons in ALS. J Mol Neurosci 2011; 43(3): 470-7.
[42]
Yacila G, Sari Y. Potential therapeutic drugs and methods for the treatment of amyotrophic lateral sclerosis. Curr Med Chem 2014; 21(31): 3583-93.
[43]
Sadeghian-Rizi T, Khanahmad H, Jahanian-Najafabadi A. Therapeutic targeting of chemokines and chemokine receptors in multiple sclerosis: opportunities and challenges. CNS Neurol Disord Drug Target 2018; 17(7): 496-508.
[44]
Lagana P, Soraci L, Gambuzza ME, Mancuso G, Delia SA. Innate immune surveillance in the central nervous system following legionella pneumophila infection. CNS Neurol Disord Drug Targets 2017; 16(10): 1080-9.
[45]
Sirivichayakul S, Kanchanatawan B, Thika S, Carvalho AF, Maes M. A new schizophrenia model: immune activation is associated with induction of different neurotoxic products which together determine memory impairments and schizophrenia symptom dimensions. CNS Neurol Disord Drug Target 2018; 18(2): 124-40.
[46]
Dibaj P, Steffens H, Zschuntzsch J, et al. In Vivo imaging reveals distinct inflammatory activity of CNS microglia versus PNS macrophages in a mouse model for ALS. PLoS One 2011; 6(3)e17910
[47]
Graber DJ, Hickey WF, Harris BT. Progressive changes in microglia and macrophages in spinal cord and peripheral nerve in the transgenic rat model of amyotrophic lateral sclerosis. J Neuroinflammation 2010; 7: 8.
[48]
Chiu IM, Phatnani H, Kuligowski M, et al. Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc Natl Acad Sci U S A 2009; 106(49): 20960-5.
[49]
Riva N, Chaabane L, Peviani M, et al. Defining peripheral nervous system dysfunction in the SOD-1G93A transgenic rat model of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2014; 73(7): 658-70.
[50]
Ji Y, Duan W, Liu Y, et al. IGF1 affects macrophage invasion and activation and TNF-alpha production in the sciatic nerves of female SOD1G93A mice. Neurosci Lett 2018; 668: 1-6.
[51]
Trias E, Ibarburu S, Barreto-Nunez R, et al. Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS. JCI Insight 2017; 2(20): 95934.
[52]
Wang Y, Liu Y, Zhai J, et al. scAAV9-VEGF-165 inhibits neuroinflammatory responses and invasion of macrophages into the peripheral nervous system of ALS transgenic mice. Brain Res Bull 2018; 140: 233-42.
[53]
Martinez-Muriana A, Mancuso R, Francos-Quijorna I, et al. CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves. Sci Rep 2016; 6: 25663.
[54]
Nardo G, Trolese MC, de Vito G, et al. Immune response in peripheral axons delays disease progression in SOD1(G93A) mice. J Neuroinflammation 2016; 13(1): 261.
[55]
Wang HA, Lee JD, Lee KM, Woodruff TM, Noakes PG. Complement C5a-C5aR1 signalling drives skeletal muscle macrophage recruitment in the hSOD1(G93A) mouse model of amyotrophic lateral sclerosis. Skelet Muscle 2017; 7(1): 10.
[56]
Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol 2014; 5: 614.
[57]
Carmans S, Hendriks JJ, Thewissen K, et al. The inhibitory neurotransmitter glycine modulates macrophage activity by activation of neutral amino acid transporters. J Neurosci Res 2010; 88(11): 2420-30.
[58]
Butovsky O, Siddiqui S, Gabriely G, et al. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 2012; 122(9): 3063-87.
[59]
Miller RG, Zhang R, Block G, et al. NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15(7-8): 601-9.
[60]
Miller RG, Block G, Katz JS, et al. Randomized phase 2 trial of NP001-a novel immune regulator: safety and early efficacy in ALS. Neurol Neuroimmunol Neuroinflamm 2015; 2(3)e100
[61]
He Y, She H, Zhang T, et al. p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1. J Cell Biol 2018; 217(1): 315-28.
[62]
She H, He Y, Zhao Y, Mao Z. Release the autophage brake on inflammation: The MAPK14/p38alpha-ULK1 pedal. Autophagy 2018; 14(6): 1097-8.
[63]
She H, He Y, Zhao Y, Mao Z. Autophagy in inflammation: the p38alpha MAPK-ULK1 axis. Macrophage 2018; 5e1629
[64]
Van Dyke JM, Smit-Oistad IM, Macrander C, Krakora D, Meyer MG, Suzuki M. Macrophage-mediated inflammation and glial response in the skeletal muscle of a rat model of familial amyotrophic lateral sclerosis (ALS). Exp Neurol 2016; 277: 275-82.
[65]
Beers DR, Zhao W, Wang J, et al. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. JCI Insight 2017; 2(5)e89530
[66]
Martinez HR, Escamilla-Ocanas CE, Camara-Lemarroy CR, Gonzalez-Garza MT, Moreno-Cuevas J, Garcia Sarreon MA. Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) in patients with amyotrophic lateral sclerosis. Neurologia 2017; 0213-4853(17): 30280-3
Call for Papers in Thematic Issues
08 May, 2024
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
30 April, 2024
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
30 April, 2024
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Drug Addiction Mechanisms in the Brain
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Advanced Pharmacy
Plant-derived Hepatoprotective Drugs
The Role of Chromenes in Drug Discovery and Development
New Avenues in Drug Discovery and Bioactive Natural Products
Practice and Re-Emergence of Herbal Medicine
Article Metrics
95
7
2
1