Neurodegenerative Diseases: New Hopes and Perspectives

doi:10.2174/1566524023666230907093451
摘要

阿尔茨海默病、帕金森氏病、肌萎缩性侧索硬化症、亨廷顿氏病和弗里德里希共济失调都是无法治愈的神经退行性疾病，其特征是不同的神经元亚型的持续进行性丧失。尽管它们在世界老龄化人口中越来越普遍，但在开发新药的同时，取得的进展却很少。最近，研究的重点已经转向发现新的治疗神经退行性疾病的药物。在这篇综述中，我们总结了最近发展的治疗方法及其在神经退行性疾病管理中的地位。
关键词: 阿尔茨海默病，帕金森病，肌萎缩侧索硬化症，亨廷顿氏病，弗里德里希共济失调，脊髓性肌萎缩症。
[1]
Tanner CM. Epidemiology of Parkinson’s disease. Neurol Clin  1992; 10(2): 317-29.
 [http://dx.doi.org/10.1016/S0733-8619(18)30212-3] [PMID: 1584176]

[2]
Armstrong R. What causes neurodegenerative disease? Folia Neuropathol  2020; 58(2): 93-112.
 [http://dx.doi.org/10.5114/fn.2020.96707] [PMID: 32729289]

[3]
Sales TA, Prandi IG, Castro AA, et al. Recent developments in metal-based drugs and chelating agents for neurodegenerative disease treatments. Int J Mol Sci  2019; 20(8): 1829.
 [http://dx.doi.org/10.3390/ijms20081829] [PMID: 31013856]

[4]
Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Invest  2005; 115(6): 1449-57.
 [http://dx.doi.org/10.1172/JCI24761] [PMID: 15931380]

[5]
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement  2007; 3(3): 186-91.
 [http://dx.doi.org/10.1016/j.jalz.2007.04.381] [PMID: 19595937]

[6]
Helder DI, Kaptein AA, Kempen GMJ, Weinman J, Houwelingen JC, Roos RAC. Living with huntington’s disease: Illness perceptions, coping mechanisms, and spouses’ quality of life. Int J Behav Med  2002; 9(1): 37-52.
 [http://dx.doi.org/10.1207/S15327558IJBM0901_03] [PMID: 12112995]

[7]
Rotermund C, Machetanz G, Fitzgerald JC. The therapeutic potential of metformin in neurodegenerative diseases. Front Endocrinol  2018; 9: 400.
 [http://dx.doi.org/10.3389/fendo.2018.00400] [PMID: 30072954]

[8]
Hainfellner JA, Wanschitz J, Jellinger K, Liberski PP, Gullotta F, Budka H. Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease. Acta Neuropathol  1998; 96(2): 116-22.
 [http://dx.doi.org/10.1007/s004010050870] [PMID: 9705125]

[9]
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science  2002; 297(5580): 353-6.

[10]
Mucke L, Selkoe DJ. Neurotoxicity of amyloid β-protein: Synaptic and network dysfunction. Cold Spring Harb Perspect Med  2012; 2(7): a006338.
 [http://dx.doi.org/10.1101/cshperspect.a006338] [PMID: 22762015]

[11]
Castello MA, Soriano S. On the origin of Alzheimer’s disease. Trials and tribulations of the amyloid hypothesis. Ageing Res Rev  2014; 13: 10-2.
 [http://dx.doi.org/10.1016/j.arr.2013.10.001] [PMID: 24252390]

[12]
Drachman DA. The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimers Dement  2014; 10(3): 372-80.
 [http://dx.doi.org/10.1016/j.jalz.2013.11.003] [PMID: 24589433]

[13]
Anand R, Gill KD, Mahdi AA. Therapeutics of Alzheimer’s disease: Past, present and future.  Neuropharmacology   2014; 76(Pt A): 27-50.
 [http://dx.doi.org/10.1016/j.neuropharm.2013.07.004] [PMID: 23891641]

[14]
Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer’s disease in later life: Longitudinal, population based study. BMJ  2001; 322(7300): 1447-51.
 [http://dx.doi.org/10.1136/bmj.322.7300.1447] [PMID: 11408299]

[15]
Abate G, Marziano M, Rungratanawanich W, Memo M, Uberti D. Nutrition and AGE-ing: Focusing on Alzheimer’s Disease. Oxid Med Cell Longev  2017; 2017: 7039816.

[16]
Kevadiya BD, Ottemann BM, Thomas MB, et al. Neurotheranostics as personalized medicines. Adv Drug Deliv Rev  2019; 148: 252-89.
 [http://dx.doi.org/10.1016/j.addr.2018.10.011] [PMID: 30421721]

[17]
Harilal S, Jose J, Parambi DGT, et al. Advancements in nanotherapeutics for Alzheimer’s disease: Current perspectives. J Pharm Pharmacol  2019; 71(9): 1370-83.
 [http://dx.doi.org/10.1111/jphp.13132] [PMID: 31304982]

[18]
Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med  2012; 366(10): 893-903.
 [http://dx.doi.org/10.1056/NEJMoa1106668] [PMID: 22397651]

[19]
Grossberg GT, Manes F, Allegri RF, et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): A multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs  2013; 27(6): 469-78.
 [http://dx.doi.org/10.1007/s40263-013-0077-7] [PMID: 23733403]

[20]
Beshir SA, Aadithsoorya AM, Parveen A, Goh SS, Hussain N, Menon VB. ADU Therapy to Treat Alzheimer’s Disease: A Narrative Review. Int J Alzheimers Dis  2022; 2022: 9343514.

[21]
Behl T, Kaur I, Sehgal A, et al. “Aducanumab” making a comeback in Alzheimer’s disease: An old wine in a new bottle. Biomed Pharmacother  2022; 148: 112746.
 [http://dx.doi.org/10.1016/j.biopha.2022.112746] [PMID: 35231697]

[22]
Knopman DS, Jones DT, Greicius MD. Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimers Dement  2021; 17(4): 696-701.
 [http://dx.doi.org/10.1002/alz.12213] [PMID: 33135381]

[23]
Arndt JW, Qian F, Smith BA, et al. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-&#946. Sci Rep  2018; 8(1): 6412.
 [http://dx.doi.org/10.1038/s41598-018-24501-0] [PMID: 29686315]

[24]
Sevigny J, Chiao P, Bussière T, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature  2016; 537(7618): 50-6.
 [http://dx.doi.org/10.1038/nature19323] [PMID: 27582220]

[25]
Gunawardena IPC, Retinasamy T, Shaikh MF. Is ADU for LMICs? promises and challenges. Brain Sci  2021; 11(11): 1547.
 [http://dx.doi.org/10.3390/brainsci11111547] [PMID: 34827546]

[26]
Cummings J, Aisen P, Lemere C, Atri A, Sabbagh M, Salloway S. Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res Ther  2021; 13(1): 98.
 [http://dx.doi.org/10.1186/s13195-021-00838-z] [PMID: 33397495]

[27]
Crehan H, Lemere CA. Anti-amyloid-β immunotherapy for Alzheimer’s disease. In: Developing Therapeutics for Alzheimer’s Disease Progress and Challenges.  Academic Press 2016; pp. 193-226.

[28]
Ferrero J, Williams L, Stella H, et al. First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer’s disease. Alzheimers Dement  2016; 2(3): 169-76.
 [http://dx.doi.org/10.1016/j.trci.2016.06.002] [PMID: 29067304]

[29]
Porsteinsson AP, Antonsdottir IM. An update on the advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother  2017; 18(6): 611-20.
 [http://dx.doi.org/10.1080/14656566.2017.1307340] [PMID: 28300462]

[30]
Minger SL, Esiri MM, McDonald B, et al. Cholinergic deficits contribute to behavioral disturbance in patients with dementia. Neurology  2000; 55(10): 1460-7.
 [http://dx.doi.org/10.1212/WNL.55.10.1460] [PMID: 11094098]

[31]
Siddique H, Hynan LS, Weiner MF. Effect of a serotonin reuptake inhibitor on irritability, apathy, and psychotic symptoms in patients with Alzheimer’s disease. J Clin Psychiatry  2009; 70(6): 915-8.
 [http://dx.doi.org/10.4088/JCP.08m04828] [PMID: 19422762]

[32]
Vermeiren Y, Van Dam D, Aerts T, Engelborghs S, De Deyn PP. Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in Alzheimer’s disease. J Alzheimers Dis  2014; 41(3): 819-33.
 [http://dx.doi.org/10.3233/JAD-140309] [PMID: 24685637]

[33]
Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: In vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther  2014; 350(3): 589-604.
 [http://dx.doi.org/10.1124/jpet.114.213793] [PMID: 24947465]

[34]
Cha DS, Luo X, Ahmed J, Becirovic L, Cha RH, McIntyre RS. Brexpiprazole as an augmentation agent to antidepressants in treatment resistant major depressive disorder. Expert Rev Neurother  2019; 19(9): 777-83.
 [http://dx.doi.org/10.1080/14737175.2019.1653759] [PMID: 31389279]

[35]
Grossberg GT, Kohegyi E, Mergel V, et al. Efficacy and safety of Brexipiprazole for the treatment of agitation in Alzheimer’s dementia: Two 12-week, randomized, double-blind, placebo-controlled trials. Am J Geriatr Psychiatry  2020; 28(4): 383-400.
 [http://dx.doi.org/10.1016/j.jagp.2019.09.009] [PMID: 31708380]

[36]
Cummings J, Ballard C, Tariot P, et al. Pimavanserin: A potential treatment for dementia-related psychosis. J Prev Alzheimers Dis  2018; 5(4): 253-8.
 [PMID: 30298184]

[37]
Vanover KE, Weiner DM, Makhay M, et al. Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther  2006; 317(2): 910-8.
 [http://dx.doi.org/10.1124/jpet.105.097006] [PMID: 16469866]

[38]
Nutt D, Stahl S, Blier P, Drago F, Zohar J, Wilson S. Inverse agonists – What do they mean for psychiatry? Eur Neuropsychopharmacol  2017; 27(1): 87-90.
 [http://dx.doi.org/10.1016/j.euroneuro.2016.11.013] [PMID: 27955830]

[39]
Kales HC, Lyketsos CG, Miller EM, Ballard C. Management of behavioral and psychological symptoms in people with Alzheimer’s disease: An international Delphi consensus. Int Psychogeriatr  2019; 31(1): 83-90.
 [http://dx.doi.org/10.1017/S1041610218000534] [PMID: 30068400]

[40]
Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: A randomised, placebo-controlled phase 3 trial. Lancet  2014; 383(9916): 533-40.
 [http://dx.doi.org/10.1016/S0140-6736(13)62106-6] [PMID: 24183563]

[41]
Ballard C, Banister C, Khan Z, et al. Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer’s disease psychosis: A phase 2, randomised, placebo-controlled, double-blind study. Lancet Neurol  2018; 17(3): 213-22.
 [http://dx.doi.org/10.1016/S1474-4422(18)30039-5] [PMID: 29452684]

[42]
Ballard C, Youakim JM, Coate B, Stankovic S. Pimavanserin in Alzheimer’s disease psychosis: Efficacy in patients with more pronounced psychotic symptoms. J Prev Alzheimers Dis  2019; 6(1): 27-33.
 [PMID: 30569083]

[43]
Ballard C, Howard R. Neuroleptic drugs in dementia: Benefits and harm. Nat Rev Neurosci  2006; 7(6): 492-500.
 [http://dx.doi.org/10.1038/nrn1926] [PMID: 16715057]

[44]
Maher AR, Maglione M, Bagley S, et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: A systematic review and meta-analysis. JAMA  2011; 306(12): 1359-69.
 [http://dx.doi.org/10.1001/jama.2011.1360] [PMID: 21954480]

[45]
Maust DT, Kim HM, Seyfried LS, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: Number needed to harm. JAMA Psychiatry  2015; 72(5): 438-45.
 [http://dx.doi.org/10.1001/jamapsychiatry.2014.3018] [PMID: 25786075]

[46]
Webster P. Pimavanserin evaluated by the FDA. Lancet  2018; 391(10132): 1762.
 [http://dx.doi.org/10.1016/S0140-6736(18)31002-X] [PMID: 29739555]

[47]
Caraci F, Santagati M, Caruso G, et al. New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer’s disease: Focus on brexpiprazole and pimavanserin. F1000 Res  2020; 9: 686.
 [http://dx.doi.org/10.12688/f1000research.22662.1] [PMID: 32695312]

[48]
Driver JA, Logroscino G, Gaziano JM, Kurth T. Incidence and remaining lifetime risk of Parkinson disease in advanced age. Neurology  2009; 72(5): 432-8.
 [http://dx.doi.org/10.1212/01.wnl.0000341769.50075.bb] [PMID: 19188574]

[49]
Tripathi KD. Essentials of Medical Pharmacology.  8th ed.. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd. 2019; pp. 426-7.

[50]
Hachinski V, Iadecola C, Petersen RC, et al. National institute of neurological disorders and stroke-canadian stroke network vascular cognitive impairment harmonization standards. Stroke  2006; 37(9): 2220-41.
 [http://dx.doi.org/10.1161/01.STR.0000237236.88823.47] [PMID: 16917086]

[51]
Rewar S. A systematic review on Parkinson’s disease (PD). IJRPB  2015; 3(2): 176.

[52]
Halperin JM, Healey DM. The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? Neurosci Biobehav Rev  2011; 35(3): 621-34.
 [http://dx.doi.org/10.1016/j.neubiorev.2010.07.006] [PMID: 20691725]

[53]
Goldman SM, Tanner C. Etiology of Parkinson’s disease Parkinson’s Disease and Movement Disorders.  London, UK: Williams and Wilkins 1998; pp. 133-58.

[54]
Schrag A, Schott JM. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol  2006; 5(4): 355-63.
 [http://dx.doi.org/10.1016/S1474-4422(06)70411-2] [PMID: 16545752]

[55]
Stoker TB, Barker RA. Recent developments in the treatment of Parkinson’s Disease. F1000 Res  2020; 9: 862.
 [http://dx.doi.org/10.12688/f1000research.25634.1] [PMID: 32789002]

[56]
Der Birkmayer WZ. L-3, 4-Dioxyphenylanine (= DOPA)-Effect bei der Parkinson-Akinese. Wien Klin Wochenschr  1961; 45: 787-8.

[57]
Trenkwalder C, Kuoppamäki M, Vahteristo M, Müller T, Ellmén J. Increased dose of carbidopa with levodopa and entacapone improves “off” time in a randomized trial. Neurology  2019; 92(13): e1487-96.
 [http://dx.doi.org/10.1212/WNL.0000000000007173] [PMID: 30824559]

[58]
Abu-Raya S, Tabakman R, Blaugrund E, Trembovler V, Lazarovici P. Neuroprotective and neurotoxic effects of monoamine oxidase-B inhibitors and derived metabolites under ischemia in PC12 cells. Eur J Pharmacol  2002; 434(3): 109-16.
 [http://dx.doi.org/10.1016/S0014-2999(01)01548-5] [PMID: 11779573]

[59]
Jankovic J, Tan EK. Parkinson’s disease: Etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry  2020; 91(8): 795-808.
 [http://dx.doi.org/10.1136/jnnp-2019-322338] [PMID: 32576618]

[60]
Hwang JY, Won JS, Nam H, Lee HW, Joo KM. Current advances in combining stem cell and gene therapy for neurodegenerative diseases. Precision and Future Medicine  2018; 2(2): 53-65.
 [http://dx.doi.org/10.23838/pfm.2018.00037]

[61]
Mittal S, Bjørnevik K, Im DS, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease.  Science  2017; 357(6354): 891-8.
 [http://dx.doi.org/10.1126/science.aaf3934] [PMID: 28860381]

[62]
Karuppagounder SS, Brahmachari S, Lee Y, Dawson VL, Dawson TM, Ko HS. The c-Abl inhibitor, Nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson’s disease. Sci Rep  2014; 4(1): 4874.
 [http://dx.doi.org/10.1038/srep04874] [PMID: 24786396]

[63]
Cai R, Zhang Y, Simmering JE, et al. Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases. J Clin Invest  2019; 129(10): 4539-49.
 [http://dx.doi.org/10.1172/JCI129987] [PMID: 31524631]

[64]
Coles LD, Tuite PJ, Öz G, et al. Repeatedí dose oral Ní acetylcysteine in Parkinson’s disease: Pharmacokinetics and effect on brain glutathione and oxidative stress. J Clin Pharmacol  2018; 58(2): 158-67.
 [http://dx.doi.org/10.1002/jcph.1008] [PMID: 28940353]

[65]
Jucaite A, Svenningsson P, Rinne JO, et al. Effect of the myeloperoxidase inhibitor AZD3241 on microglia: A PET study in Parkinson’s disease. Brain  2015; 138(9): 2687-700.
 [http://dx.doi.org/10.1093/brain/awv184] [PMID: 26137956]

[66]
Garea-Rodríguez E, Eesmaa A, Lindholm P, et al. Comparative analysis of the effects of neurotrophic factors CDNF and GDNF in a nonhuman primate model of Parkinson’s disease. PLoS One  2016; 11(2): e0149776.
 [http://dx.doi.org/10.1371/journal.pone.0149776] [PMID: 26901822]

[67]
Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide addí on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord  2014; 29(2): 229-37.
 [http://dx.doi.org/10.1002/mds.25751] [PMID: 24323641]

[68]
Kim SD, Allen NE, Canning CG, Fung VSC. Postural instability in patients with Parkinson’s disease. Epidemiology, pathophysiology and management. CNS Drugs  2013; 27(2): 97-112.
 [http://dx.doi.org/10.1007/s40263-012-0012-3] [PMID: 23076544]

[69]
(a) Kumakura Y, Danielsen EH, Gjedde A, et al. Elevated [18F] FDOPA utilization in the periaqueductal grey and medial nucleus accumbens of patients with early Parkinson’s disease. Neuroimage  2010; 49(4): 2933-9.; 
(b) Gross LA. Occupational therapy involvement in interdisciplinary palliative care for individuals with dementia Doctoral dissertation, Boston University 2019.

[70]
Sellnow RC, Newman JH, Chambers N, et al. Regulation of dopamine neurotransmission from serotonergic neurons by ectopic expression of the dopamine D2 autoreceptor blocks levodopa-induced dyskinesia. Acta Neuropathol Commun  2019; 7(1): 8.
 [http://dx.doi.org/10.1186/s40478-018-0653-7] [PMID: 30646956]

[71]
Luk KC, Kehm V, Carroll J, et al. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science  2012; 338(6109): 949-53.
 [http://dx.doi.org/10.1126/science.1227157] [PMID: 23161999]

[72]
Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting alpha-Synuclein as a therapy for Parkinson’s disease. Front Mol Neurosci  2019; 12: 299.
 [http://dx.doi.org/10.3389/fnmol.2019.00299] [PMID: 31866823]

[73]
McCormack AL, Mak SK, Henderson JM, Bumcrot D, Farrer MJ, Di Monte DA. α-synuclein suppression by targeted small interfering RNA in the primate substantia nigra. PLoS One  2010; 5(8): e12122.
 [http://dx.doi.org/10.1371/journal.pone.0012122] [PMID: 20711464]

[74]
Weihofen A, Liu Y, Arndt JW, et al. Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models. Neurobiol Dis  2019; 124: 276-88.
 [http://dx.doi.org/10.1016/j.nbd.2018.10.016] [PMID: 30381260]

[75]
Brys M, Fanning L, Hung S, et al. Randomized phase I clinical trial of anti–αí synuclein antibody BIIB054. Mov Disord  2019; 34(8): 1154-63.
 [http://dx.doi.org/10.1002/mds.27738] [PMID: 31211448]

[76]
Bergstrand A, Hansson FS, Trifunovic A, et al. Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells. Biochem Biophys Res Commun  2006; 342(1): 330-5.
 [http://dx.doi.org/10.1016/j.bbrc.2006.01.148] [PMID: 16480958]

[77]
Barker RA, Parmar M, Studer L, Takahashi J. Human trials of stem cell-derived dopamine neurons for Parkinson’s disease: Dawn of a new era. Cell Stem Cell  2017; 21(5): 569-73.
 [http://dx.doi.org/10.1016/j.stem.2017.09.014] [PMID: 29100010]

[78]
Christine CW, Bankiewicz KS, Van Laar AD, et al. Magnetic resonance imaging–guided phase 1 trial of putaminal AADC gene therapy for Parkinson’s disease. Ann Neurol  2019; 85(5): 704-14.
 [http://dx.doi.org/10.1002/ana.25450] [PMID: 30802998]

[79]
Palfi S, Gurruchaga JM, Ralph GS, et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: A dose escalation, open-label, phase 1/2 trial. Lancet  2014; 383(9923): 1138-46.
 [http://dx.doi.org/10.1016/S0140-6736(13)61939-X] [PMID: 24412048]

[80]
Zheng Z, Chen J, Chopp M. Mechanisms of plasticity remodeling and recovery. In: Stroke.   2021; pp. 129-137.e.

[81]
Ross CA, Aylward EH, Wild EJ, et al. Huntington disease: Natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol  2014; 10(4): 204-16.
 [http://dx.doi.org/10.1038/nrneurol.2014.24] [PMID: 24614516]

[82]
Lee JK, Conrad A, Epping E, et al. Effect of trinucleotide repeats in the Huntington’s gene on intelligence. EBioMedicine  2018; 31: 47-53.
 [http://dx.doi.org/10.1016/j.ebiom.2018.03.031] [PMID: 29685790]

[83]
Sun YM, Zhang YB, Wu ZY. Huntington’s disease: The relationship between phenotype and genotype. Mol Neurobiol  2017; 54(1): 342-8.
 [http://dx.doi.org/10.1007/s12035-015-9662-8] [PMID: 26742514]

[84]
Telenius H, Kremer B, Goldberg YP, et al. Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nat Genet  1994; 6(4): 409-14.
 [http://dx.doi.org/10.1038/ng0494-409] [PMID: 8054984]

[85]
Bright LJN, Akila R. Huntington’s disease: Current advances and future prospects. Int J Pharma Sci  2021; 13(12)

[86]
Arning L, Nguyen HP. Huntington disease update: New insights into the role of repeat instability in disease pathogenesis. Med Genetik  2022; 33(4): 293-300.
 [http://dx.doi.org/10.1515/medgen-2021-2101]

[87]
Raymond LA, André VM, Cepeda C, Gladding CM, Milnerwood AJ, Levine MS. Pathophysiology of Huntington’s disease: Time-dependent alterations in synaptic and receptor function. Neuroscience  2011; 198: 252-73.
 [http://dx.doi.org/10.1016/j.neuroscience.2011.08.052] [PMID: 21907762]

[88]
Krishnendu PR, Arjun B, Vibina K. Review on evaluating the role of nsaids for the treatment of alzheimer’s disease. Int J Appl Pharm  2021; 13(1): 91-4.

[89]
Bates GP, Dorsey R, Gusella JF, et al. Huntington disease. Nat Rev Dis Primers  2015; 1(1): 15005.
 [http://dx.doi.org/10.1038/nrdp.2015.5] [PMID: 27188817]

[90]
Frank S. Tetrabenazine as anti-chorea therapy in Huntington Disease: An open-label continuation study. BMC Neurol  2009; 9(1): 62-72.
 [http://dx.doi.org/10.1186/1471-2377-9-62] [PMID: 20021666]

[91]
Paleacu D. Tetrabenazine in the treatment of Huntington’s disease. Neuropsychiatr Dis Treat  2007; 3(5): 545-51.
 [PMID: 19381278]

[92]
Mehvar R, Jamali F. Concentration-effect relationships of tetrabenazine and dihydrotetrabenazine in the rat. J Pharm Sci  1987; 76(6): 461-5.
 [http://dx.doi.org/10.1002/jps.2600760610] [PMID: 3625491]

[93]
Thibaut F, Faucheux BA, Marquez J, et al. Regional distribution of monoamine vesicular uptake sites in the mesencephalon of control subjects and patients with Parkinson’s disease: A postmortem study using tritiated tetrabenazine. Brain Res  1995; 692(1-2): 233-43.
 [http://dx.doi.org/10.1016/0006-8993(95)00674-F] [PMID: 8548309]

[94]
Kenney C, Hunter C, Davidson A, Jankovic J. Short-term effects of tetrabenazine on chorea associated with Huntington’s disease. Mov Disord  2007; 22(1): 10-3.
 [http://dx.doi.org/10.1002/mds.21161] [PMID: 17078062]

[95]
Scherman D, Henry JP. Reserpine binding to bovine chromaffin granule membranes. Characterization and comparison with dihydrotetrabenazine binding. Mol Pharmacol  1984; 25(1): 113-22.
 [PMID: 6708929]

[96]
Quinn N, Marsden CD. A double blind trial of sulpiride in Huntington’s disease and tardive dyskinesia. J Neurol Neurosurg Psychiatry  1984; 47(8): 844-7.
 [http://dx.doi.org/10.1136/jnnp.47.8.844] [PMID: 6236286]

[97]
Deroover J, Baro F, Bourguignon RP, Smets P. Tiapride versus placebo: A double-blind comparative study in the management of Huntington’s chorea. Curr Med Res Opin  1984; 9(5): 329-38.
 [http://dx.doi.org/10.1185/03007998409109601] [PMID: 6241563]

[98]
Leonard DP, Kidson MA, Brown JGE, Shannon PJ, Taryan S. A double blind trial of lithium carbonate and haloperidol in Huntington’s chorea. Aust N Z J Psychiatry  1975; 9(2): 115-8.
 [http://dx.doi.org/10.3109/00048677509159834] [PMID: 125578]

[99]
Barr AN, Fischer JH, Roller WC, Spunt AL, Singhal A. Serum haloperidol concentration and choreiform movements in Huntington’s disease. Neurology  1988; 38(1): 84-8.
 [http://dx.doi.org/10.1212/WNL.38.1.84] [PMID: 2962009]

[100]
Bonelli RM, Mahnert FA, Niederwieser G. Olanzapine for Huntington’s disease: An open label study. Clinical neuropharmacology. 2002 Sep 1;25(5):263-5. Squitieri F, Cannella M, Porcellini A, Brusa L, Simonelli M, Ruggieri S. Short-term effects of olanzapine in Huntington disease. Cogn Behav Neurol  2001; 14(1): 69-72.

[101]
Peiris JB, Boralessa H, Lionel ND. Clonazepam in the treatment of choreiform activity. Med J Aust  1976; 1(8): 225-7.
 [http://dx.doi.org/10.5694/j.1326-5377.1976.tb140550.x] [PMID: 131236]

[102]
Eddy CM, Parkinson EG, Rickards HE. Changes in mental state and behaviour in Huntington’s disease. Lancet Psychiatry  2016; 3(11): 1079-86.
 [http://dx.doi.org/10.1016/S2215-0366(16)30144-4] [PMID: 27663851]

[103]
Li Y, Hai S, Zhou Y, Dong BR. Cholinesterase inhibitors for rarer dementias associated with neurological conditions. Cochrane Database Syst Rev  2015; 3(3): CD009444.
 [http://dx.doi.org/10.1002/14651858.CD009444.pub3]

[104]
Beglinger LJ, Adams WH, Langbehn D, et al. Results of the citalopram to enhance cognition in Huntington disease trial. Mov Disord  2014; 29(3): 401-5.
 [http://dx.doi.org/10.1002/mds.25750] [PMID: 24375941]

[105]
Kumar A, Kumar V, Singh K, et al. Therapeutic advances for Huntington’s disease. Brain Sci  2020; 10(1): 43.
 [http://dx.doi.org/10.3390/brainsci10010043] [PMID: 31940909]

[106]
Moreno-Delgado D, Puigdellívol M, Moreno E, et al. Modulation of dopamine D1 receptors via histamine H3 receptors is a novel therapeutic target for Huntington’s disease. eLife  2020; 9: e51093.
 [http://dx.doi.org/10.7554/eLife.51093] [PMID: 32513388]

[107]
Lum PT, Sekar M, Gan SH, Bonam SR, Shaikh MF. Protective effect of natural products against Huntington’s disease: An overview of scientific evidence and understanding their mechanism of action. ACS Chem Neurosci  2021; 12(3): 391-418.
 [http://dx.doi.org/10.1021/acschemneuro.0c00824] [PMID: 33475334]

[108]
Sharma A, Behl T, Sharma L, Aelya L, Bungau S. Mitochondrial dysfunction in huntington’s disease: Pathogenesis and therapeutic opportunities. Curr Drug Targets  2021; 22(14): 1637-67.
 [http://dx.doi.org/10.2174/1389450122666210224105945] [PMID: 33655829]

[109]
Chen M, Ona VO, Li M, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med  2000; 6(7): 797-801.
 [http://dx.doi.org/10.1038/77528] [PMID: 10888929]

[110]
Bonelli RM, Hödl AK, Hofmann P, Kapfhammer HP. Neuroprotection in Huntington’s disease: A 2-year study on minocycline. Int Clin Psychopharmacol  2004; 19(6): 337-42.
 [http://dx.doi.org/10.1097/00004850-200411000-00004] [PMID: 15486519]

[111]
Thomas M, Ashizawa T, Jankovic J. Minocycline in Huntington’s disease: A pilot study. Mov Disord  2004; 19(6): 692-5.
 [http://dx.doi.org/10.1002/mds.20018] [PMID: 15197710]

[112]
Ravikumar B, Vacher C, Berger Z, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet  2004; 36(6): 585-95.
 [http://dx.doi.org/10.1038/ng1362] [PMID: 15146184]

[113]
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell  2017; 168(6): 960-76.
 [http://dx.doi.org/10.1016/j.cell.2017.02.004] [PMID: 28283069]

[114]
Sánchez I, Mahlke C, Yuan J. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature  2003; 421(6921): 373-9.
 [http://dx.doi.org/10.1038/nature01301] [PMID: 12540902]

[115]
Tanaka M, Machida Y, Niu S, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med  2004; 10(2): 148-54.
 [http://dx.doi.org/10.1038/nm985] [PMID: 14730359]

[116]
Chopra V, Fox JH, Lieberman G, et al. A small-molecule therapeutic lead for Huntington’s disease: Preclinical pharmacology and efficacy of C2-8 in the R6/2 transgenic mouse. Proc Natl Acad Sci  2007; 104(42): 16685-9.
 [http://dx.doi.org/10.1073/pnas.0707842104] [PMID: 17925440]

[117]
Mao Z, Choo YS, Lesort M. Cystamine and cysteamine prevent 3-NP-induced mitochondrial depolarization of Huntington’s disease knock-in striatal cells. Eur J Neurosci  2006; 23(7): 1701-10.
 [http://dx.doi.org/10.1111/j.1460-9568.2006.04686.x] [PMID: 16623826]

[118]
Gohil VM, Offner N, Walker JA, et al. Meclizine is neuroprotective in models of Huntington’s disease. Hum Mol Genet  2011; 20(2): 294-300.
 [http://dx.doi.org/10.1093/hmg/ddq464] [PMID: 20977989]

[119]
Ferreira JJ, Rosser A, Craufurd D, Squitieri F, Mallard N, Landwehrmeyer B. Ethyl-eicosapentaenoic acid treatment in Huntington’s disease: A placebo-controlled clinical trial. Mov Disord  2015; 30(10): 1426-9.
 [http://dx.doi.org/10.1002/mds.26308] [PMID: 26175332]

[120]
Hersch SM, Schifitto G, Oakes D, et al. The CREST-E study of creatine for Huntington disease. Neurology  2017; 89(6): 594-601.
 [http://dx.doi.org/10.1212/WNL.0000000000004209] [PMID: 28701493]

[121]
Ryu H, Lee J, Hagerty SW, et al. ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington’s disease. Proc Natl Acad Sci  2006; 103(50): 19176-81.
 [http://dx.doi.org/10.1073/pnas.0606373103] [PMID: 17142323]

[122]
Hockly E, Richon VM, Woodman B, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci USA  2003; 100(4): 2041-6.
 [http://dx.doi.org/10.1073/pnas.0437870100] [PMID: 12576549]

[123]
Gardian G, Browne SE, Choi DK, et al. Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington’s disease. J Biol Chem  2005; 280(1): 556-63.
 [http://dx.doi.org/10.1074/jbc.M410210200] [PMID: 15494404]

[124]
Thomas EA, Coppola G, Desplats PA, et al. The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington’s disease transgenic mice. Proc Natl Acad Sci  2008; 105(40): 15564-9.
 [http://dx.doi.org/10.1073/pnas.0804249105] [PMID: 18829438]

[125]
Harper SQ, Staber PD, He X, et al. RNA interference improves motor and neuropathological abnormalities in a Huntington’s disease mouse model. Proc Natl Acad Sci  2005; 102(16): 5820-5.
 [http://dx.doi.org/10.1073/pnas.0501507102] [PMID: 15811941]

[126]
Stanek LM, Sardi SP, Mastis B, et al. Silencing mutant huntingtin by adeno-associated virus-mediated RNA interference ameliorates disease manifestations in the YAC128 mouse model of Huntington’s disease. Hum Gene Ther  2014; 25(5): 461-74.
 [http://dx.doi.org/10.1089/hum.2013.200] [PMID: 24484067]

[127]
Samaranch L, Blits B, San Sebastian W, et al. MR-guided parenchymal delivery of adeno-associated viral vector serotype 5 in non-human primate brain. Gene Ther  2017; 24(4): 253-61.
 [http://dx.doi.org/10.1038/gt.2017.14] [PMID: 28300083]

[128]
Franich NR, Fitzsimons HL, Fong DM, Klugmann M, During MJ, Young D. AAV vector-mediated RNAi of mutant huntingtin expression is neuroprotective in a novel genetic rat model of Huntington’s disease. Mol Ther  2008; 16(5): 947-56.
 [http://dx.doi.org/10.1038/mt.2008.50] [PMID: 18388917]

[129]
Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron  2012; 74(6): 1031-44.
 [http://dx.doi.org/10.1016/j.neuron.2012.05.009] [PMID: 22726834]

[130]
Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol  2010; 50(1): 259-93.
 [http://dx.doi.org/10.1146/annurev.pharmtox.010909.105654] [PMID: 20055705]

[131]
Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: Prospects and challenges. Nat Med  2015; 21(2): 121-31.
 [http://dx.doi.org/10.1038/nm.3793] [PMID: 25654603]

[132]
Yang S, Chang R, Yang H, et al. CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. J Clin Invest  2017; 127(7): 2719-24.
 [http://dx.doi.org/10.1172/JCI92087] [PMID: 28628038]

[133]
Garriga-Canut M, Agustín-Pavón C, Herrmann F, et al. Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice. Proc Natl Acad Sci USA  2012; 109(45): E3136-45.
 [http://dx.doi.org/10.1073/pnas.1206506109] [PMID: 23054839]

[134]
Graham RK, Deng Y, Slow EJ, et al. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell  2006; 125(6): 1179-91.
 [http://dx.doi.org/10.1016/j.cell.2006.04.026] [PMID: 16777606]

[135]
Wellington CL, Ellerby LM, Hackam AS, et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem  1998; 273(15): 9158-67.
 [http://dx.doi.org/10.1074/jbc.273.15.9158] [PMID: 9535906]

[136]
Reilmann R, Rouzade-Dominguez ML, Saft C, et al. A randomized, placeboí controlled trial of AFQ056 for the treatment of chorea in Huntington’s disease. Mov Disord  2015; 30(3): 427-31.
 [http://dx.doi.org/10.1002/mds.26174] [PMID: 25689146]

[137]
Klivenyi P, Ferrante RJ, Gardian G, Browne S, Chabrier PE, Beal MF. Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington’s disease. J Neurochem  2003; 86(1): 267-72.
 [http://dx.doi.org/10.1046/j.1471-4159.2003.t01-1-01868.x] [PMID: 12807446]

[138]
Chabrier PE, Auguet M. Pharmacological properties of BN82451: A novel multitargeting neuroprotective agent. CNS Drug Rev  2007; 13(3): 317-32.
 [http://dx.doi.org/10.1111/j.1527-3458.2007.00018.x] [PMID: 17894648]

[139]
Thulasiraman V, Yang CF, Frydman J. In vivo newly translated polypeptides are sequestered in a protected folding environment. EMBO J  1999; 18(1): 85-95.
 [http://dx.doi.org/10.1093/emboj/18.1.85] [PMID: 9878053]

[140]
Kalisman N, Adams CM, Levitt M. Subunit order of eukaryotic TRiC/CCT chaperonin by cross-linking, mass spectrometry, and combinatorial homology modeling. Proc Natl Acad Sci USA  2012; 109(8): 2884-9.
 [http://dx.doi.org/10.1073/pnas.1119472109] [PMID: 22308438]

[141]
Safren N, El Ayadi A, Chang L, et al. Ubiquilin-1 overexpression increases the lifespan and delays accumulation of Huntingtin aggregates in the R6/2 mouse model of Huntington’s disease. PLoS One  2014; 9(1): e87513.
 [http://dx.doi.org/10.1371/journal.pone.0087513] [PMID: 24475300]

[142]
Marder K, Gu Y, Eberly S, et al. Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease. JAMA Neurol  2013; 70(11): 1382-8.
 [http://dx.doi.org/10.1001/jamaneurol.2013.3487] [PMID: 24000094]

[143]
Beister A, Kraus P, Kuhn W, Dose M, Weindl A, Gerlach M. The N-methyl-D-aspartate antagonist memantine retards progression of Huntington’s disease. In: Focus on extrapyramidal dysfunction.  Vienna: Springer 2004; pp. 117-22.

[144]
Lee ST, Chu K, Park JE, et al. Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington’s disease. Brain Res  2006; 1118(1): 199-207.
 [http://dx.doi.org/10.1016/j.brainres.2006.08.035] [PMID: 16959224]

[145]
Cankurtaran ES, Ozalp E, Soygur H, Cakir A. Clinical experience with risperidone and memantine in the treatment of Huntington’s disease. J Natl Med Assoc  2006; 98(8): 1353-5.
 [PMID: 16916137]

[146]
Dau A, Gladding CM, Sepers MD, Raymond LA. Chronic blockade of extrasynaptic NMDA receptors ameliorates synaptic dysfunction and pro-death signaling in Huntington disease transgenic mice. Neurobiol Dis  2014; 62: 533-42.
 [http://dx.doi.org/10.1016/j.nbd.2013.11.013] [PMID: 24269729]

[147]
Okamoto S, Pouladi MA, Talantova M, et al. Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat Med  2009; 15(12): 1407-13.
 [http://dx.doi.org/10.1038/nm.2056] [PMID: 19915593]

[148]
Milnerwood AJ, Gladding CM, Pouladi MA, et al. Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington’s disease mice. Neuron  2010; 65(2): 178-90.
 [http://dx.doi.org/10.1016/j.neuron.2010.01.008] [PMID: 20152125]

[149]
Palfi S, Riche D, Brouillet E, et al. Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration. Exp Neurol  1997; 146(1): 135-41.
 [http://dx.doi.org/10.1006/exnr.1997.6520] [PMID: 9225746]

[150]
Landwehrmeyer GB, Dubois B, de Yébenes JG, et al. Riluzole in Huntington’s disease: A 3-year, randomized controlled study. Ann Neurol  2007; 62(3): 262-72.
 [http://dx.doi.org/10.1002/ana.21181] [PMID: 17702031]

[151]
Wang H, Chen X, Li Y, Tang TS, Bezprozvanny I. Tetrabenazine is neuroprotective in Huntington’s disease mice. Mol Neurodegener  2010; 5(1): 18.
 [http://dx.doi.org/10.1186/1750-1326-5-18] [PMID: 20420689]

[152]
Coppen EM, Roos RAC. Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs  2017; 77(1): 29-46.
 [http://dx.doi.org/10.1007/s40265-016-0670-4] [PMID: 27988871]

[153]
de Tommaso M, Serpino C, Sciruicchio V. Management of Huntington’s disease: Role of tetrabenazine. Ther Clin Risk Manag  2011; 7: 123-9.
 [http://dx.doi.org/10.2147/TCRM.S17152] [PMID: 21479143]

[154]
Claassen DO, Carroll B, De Boer LM, et al. Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease. J Clin Mov Disord  2017; 4(1): 3.
 [http://dx.doi.org/10.1186/s40734-017-0051-5] [PMID: 28265459]

[155]
Bonelli RM, Heuberger C, Reisecker F. Minocycline for Huntington’s disease: An open label study. Neurology  2003; 60(5): 883-4.
 [http://dx.doi.org/10.1212/01.WNL.0000049936.85487.7A] [PMID: 12629257]

[156]
Frid P, Anisimov SV, Popovic N. Congo red and protein aggregation in neurodegenerative diseases. Brain Res Brain Res Rev  2007; 53(1): 135-60.
 [http://dx.doi.org/10.1016/j.brainresrev.2006.08.001] [PMID: 16959325]

[157]
McGowan DP, van Roon-Mom W, Holloway H, et al. Amyloid-like inclusions in Huntington’s disease. Neuroscience  2000; 100(4): 677-80.
 [http://dx.doi.org/10.1016/S0306-4522(00)00391-2] [PMID: 11036200]

[158]
Lee HJ, Yoon YS, Lee SJ. Mechanism of neuroprotection by trehalose: Controversy surrounding autophagy induction. Cell Death Dis  2018; 9(7): 712.
 [http://dx.doi.org/10.1038/s41419-018-0749-9] [PMID: 29907758]

[159]
Fernandez-Estevez MA, Casarejos MJ, López Sendon J, et al. Trehalose reverses cell malfunction in fibroblasts from normal and Huntington’s disease patients caused by proteosome inhibition. PLoS One  2014; 9(2): e90202.
 [http://dx.doi.org/10.1371/journal.pone.0090202] [PMID: 24587280]

[160]
Wang N, Lu XH, Sandoval SV, Yang XW. An independent study of the preclinical efficacy of C2-8 in the R6/2 transgenic mouse model of Huntington’s disease. J Huntingtons Dis  2013; 2(4): 443-51.
 [http://dx.doi.org/10.3233/JHD-130074] [PMID: 25062731]

[161]
Pryor WM, Biagioli M, Shahani N, et al. Huntingtin promotes mTORC1 signaling in the pathogenesis of Huntington’s disease. Sci Signal  2014; 7(349): ra103.
 [http://dx.doi.org/10.1126/scisignal.2005633] [PMID: 25351248]

[162]
Ryu H, Rosas HD, Hersch SM, Ferrante RJ. The therapeutic role of creatine in Huntington’s disease. Pharmacol Ther  2005; 108(2): 193-207.
 [http://dx.doi.org/10.1016/j.pharmthera.2005.04.008] [PMID: 16055197]

[163]
Hersch SM, Gevorkian S, Marder K, et al. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG. Neurology  2006; 66(2): 250-2.
 [http://dx.doi.org/10.1212/01.wnl.0000194318.74946.b6] [PMID: 16434666]

[164]
Verbessem P, Lemiere J, Eijnde BO, et al. Creatine supplementation in Huntington’s disease: A placebo-controlled pilot trial. Neurology  2003; 61(7): 925-30.
 [http://dx.doi.org/10.1212/01.WNL.0000090629.40891.4B] [PMID: 14557561]

[165]
Andrich J, Saft C, Gerlach M, et al. Coenzyme Q 10 serum levels in Huntington’s disease. In: Focus on Extrapyramidal Dysfunction.  Vienna: Springer 2004; pp. 111-6.

[166]
Ferrante RJ, Andreassen OA, Dedeoglu A, et al. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington’s disease. J Neurosci  2002; 22(5): 1592-9.
 [http://dx.doi.org/10.1523/JNEUROSCI.22-05-01592.2002] [PMID: 11880489]

[167]
Yang L, Calingasan NY, Wille EJ, et al. Combination therapy with Coenzyme Q 10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases. J Neurochem  2009; 109(5): 1427-39.
 [http://dx.doi.org/10.1111/j.1471-4159.2009.06074.x] [PMID: 19476553]

[168]
Jump DB. The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem  2002; 277(11): 8755-8.
 [http://dx.doi.org/10.1074/jbc.R100062200] [PMID: 11748246]

[169]
Lonergan PE, Martin DSD, Horrobin DF, Lynch MA. Neuroprotective effect of eicosapentaenoic acid in hippocampus of rats exposed to γ-irradiation. J Biol Chem  2002; 277(23): 20804-11.
 [http://dx.doi.org/10.1074/jbc.M202387200] [PMID: 11912218]

[170]
Martin DSD, Lonergan PE, Boland B, et al. Apoptotic changes in the aged brain are triggered by interleukin-1β-induced activation of p38 and reversed by treatment with eicosapentaenoic acid. J Biol Chem  2002; 277(37): 34239-46.
 [http://dx.doi.org/10.1074/jbc.M205289200] [PMID: 12091394]

[171]
Puri BK, Leavitt BR, Hayden MR, et al. Ethyl-EPA in Huntington disease: A double-blind, randomized, placebo-controlled trial. Neurology  2005; 65(2): 286-92.
 [http://dx.doi.org/10.1212/01.wnl.0000169025.09670.6d] [PMID: 16043801]

[172]
Huntington Study Group TREND-HD Investigators. Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: The TREND-HD study. Arch Neurol  2008; 65(12): 1582-9.
 [PMID: 19064745]

[173]
Hogarth P, Lovrecic L, Krainc D. Sodium phenylbutyrate in Huntington’s disease: A dose-finding study. Mov Disord  2007; 22(13): 1962-4.
 [http://dx.doi.org/10.1002/mds.21632] [PMID: 17702032]

[174]
Hockly E, Richon VM, Woodman B, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci  2003; 100(4): 2041-6.
 [http://dx.doi.org/10.1073/pnas.0437870100] [PMID: 12576549]

[175]
Sah DWY, Aronin N. Oligonucleotide therapeutic approaches for Huntington disease. J Clin Invest  2011; 121(2): 500-7.
 [http://dx.doi.org/10.1172/JCI45130] [PMID: 21285523]

[176]
Miniarikova J, Evers MM, Konstantinova P. Translation of microRNA-based huntingtin-lowering therapies from preclinical studies to the clinic. Mol Ther  2018; 26(4): 947-62.
 [http://dx.doi.org/10.1016/j.ymthe.2018.02.002] [PMID: 29503201]

[177]
Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol  2017; 16(10): 837-47.
 [http://dx.doi.org/10.1016/S1474-4422(17)30280-6] [PMID: 28920889]

[178]
Boudreau RL, McBride JL, Martins I, et al. Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington’s disease mice. Mol Ther  2009; 17(6): 1053-63.
 [http://dx.doi.org/10.1038/mt.2009.17] [PMID: 19240687]

[179]
Marelli C, Maschat F. The P42 peptide and Peptide-based therapies for Huntington’s disease. Orphanet J Rare Dis  2016; 11(1): 24.
 [http://dx.doi.org/10.1186/s13023-016-0405-3] [PMID: 26984770]

[180]
Malankhanova TB, Malakhova AA, Medvedev SP, Zakian SM. Modern genome editing technologies in Huntington’s disease research. J Huntingtons Dis  2017; 6(1): 19-31.
 [http://dx.doi.org/10.3233/JHD-160222] [PMID: 28128770]

[181]
Dabrowska M, Olejniczak M. Gene therapy for Huntington’s disease using targeted endonucleases. In: Trinucleotide Repeats.  New York, NY: Humana 2020; pp. 269-84.

[182]
Ekman FK, Ojala DS, Adil MM, Lopez PA, Schaffer DV, Gaj T. CRISPR-Cas9-mediated genome editing increases lifespan and improves motor deficits in a Huntington’s disease mouse model. Mol Ther Nucleic Acids  2019; 17: 829-39.
 [http://dx.doi.org/10.1016/j.omtn.2019.07.009] [PMID: 31465962]

[183]
Caron NS, Dorsey ER, Hayden MR. Therapeutic approaches to Huntington disease: From the bench to the clinic. Nat Rev Drug Discov  2018; 17(10): 729-50.
 [http://dx.doi.org/10.1038/nrd.2018.133] [PMID: 30237454]

[184]
Pattison LR, Kotter MR, Fraga D, Bonelli RM. Apoptotic cascades as possible targets for inhibiting cell death in Huntington’s disease. J Neurol  2006; 253(9): 1137-42.
 [http://dx.doi.org/10.1007/s00415-006-0198-8] [PMID: 16998646]

[185]
Sofi F, Macchi C, Casini A. Mediterranean diet and minimizing neurodegeneration. Curr Nutr Rep  2013; 2(2): 75-80.
 [http://dx.doi.org/10.1007/s13668-013-0041-7]

[186]
Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement  2015; 11(9): 1007-14.
 [http://dx.doi.org/10.1016/j.jalz.2014.11.009] [PMID: 25681666]

[187]
Ehrnhoefer DE, Martin DD, Schmidt ME, et al. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease. Acta Neuropathol Commun  2018; 6(1): 16.
 [http://dx.doi.org/10.1186/s40478-018-0518-0]

[188]
Hardiman O, Al-Chalabi A, Chio A, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers  2017; 3(1): 1-9.

[189]
Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. N Engl J Med  2017; 377(172): 2.

[190]
Wijesekera LC, Nigel LP. Amyotrophic lateral sclerosis. Orphanet J Rare Dis  2009; 4(1): 3.
 [http://dx.doi.org/10.1186/1750-1172-4-3] [PMID: 19192301]

[191]
Phukan J, Pender NP, Hardiman O. Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol  2007; 6(11): 994-1003.
 [http://dx.doi.org/10.1016/S1474-4422(07)70265-X] [PMID: 17945153]

[192]
Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology  1998; 51(6): 1546-54.
 [http://dx.doi.org/10.1212/WNL.51.6.1546] [PMID: 9855500]

[193]
Burrell JR, Kiernan MC, Vucic S, Hodges JR. Motor Neuron dysfunction in frontotemporal dementia. Brain  2011; 134(9): 2582-94.
 [http://dx.doi.org/10.1093/brain/awr195] [PMID: 21840887]

[194]
Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science  2006; 314(5796): 130-3.
 [http://dx.doi.org/10.1126/science.1134108] [PMID: 17023659]

[195]
Ryan M, Heverin M, McLaughlin RL, Hardiman O. Lifetime risk and heritability of amyotrophic lateral sclerosis. JAMA Neurol  2019; 76(11): 1367-74.
 [http://dx.doi.org/10.1001/jamaneurol.2019.2044] [PMID: 31329211]

[196]
Al-Chalabi A, Fang F, Hanby MF, et al. An estimate of amyotrophic lateral sclerosis heritability using twin data. J Neurol Neurosurg Psychiatry  2010; 81(12): 1324-6.
 [http://dx.doi.org/10.1136/jnnp.2010.207464] [PMID: 20861059]

[197]
Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature  1993; 362(6415): 59-62.
 [http://dx.doi.org/10.1038/362059a0] [PMID: 8446170]

[198]
Sreedharan J, Blair IP, Tripathi VB, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science  2008; 319(5870): 1668-72.
 [http://dx.doi.org/10.1126/science.1154584] [PMID: 18309045]

[199]
Kabashi E, Valdmanis PN, Dion P, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet  2008; 40(5): 572-4.
 [http://dx.doi.org/10.1038/ng.132] [PMID: 18372902]

[200]
Kwiatkowski TJ Jr, Bosco DA, LeClerc AL, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science  2009; 323(5918): 1205-8.
 [http://dx.doi.org/10.1126/science.1166066] [PMID: 19251627]

[201]
Cirulli ET, Lasseigne BN, Petrovski S, et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science  2015; 347(6229): 1436-41.
 [http://dx.doi.org/10.1126/science.aaa3650] [PMID: 25700176]

[202]
Freischmidt A, Wieland T, Richter B, et al. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci  2015; 18(5): 631-6.
 [http://dx.doi.org/10.1038/nn.4000] [PMID: 25803835]

[203]
Le Ber I, De Septenville A, Millecamps S, et al. TBK1 mutation frequencies in French frontotemporal dementia and amyotrophic lateral sclerosis cohorts. Neurobiol Aging  2015; 36(11): 3116.e5-8.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2015.08.009] [PMID: 26476236]

[204]
Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med  1994; 330(9): 585-91.
 [http://dx.doi.org/10.1056/NEJM199403033300901] [PMID: 8302340]

[205]
Doble A. The pharmacology and mechanism of action of riluzole. Neurology  1996; 47(6) (Suppl. 4): 233S-41S.
 [http://dx.doi.org/10.1212/WNL.47.6_Suppl_4.233S] [PMID: 8959995]

[206]
Grant P, Song JY, Swedo SE. Review of the use of the glutamate antagonist riluzole in psychiatric disorders and a description of recent use in childhood obsessive-compulsive disorder. J Child Adolesc Psychopharmacol  2010; 20(4): 309-15.
 [http://dx.doi.org/10.1089/cap.2010.0009] [PMID: 20807069]

[207]
Schultz J. Disease-modifying treatment of amyotrophic lateral sclerosis. Am J Manag Care  2018; 24(S15): S327-35.
 [PMID: 30207671]

[208]
Lacomblez L, Bensimon G, Meininger V, Leigh PN, Guillet P. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet  1996; 347(9013): 1425-31.
 [http://dx.doi.org/10.1016/S0140-6736(96)91680-3] [PMID: 8676624]

[209]
Hinchcliffe M, Smith A. Riluzole: Real-world evidence supports significant extension of median survival times in patients with amyotrophic lateral sclerosis. Degener Neurol Neuromuscul Dis  2017; 7: 61-70.
 [http://dx.doi.org/10.2147/DNND.S135748] [PMID: 30050378]

[210]
Cruz MP. Edaravone (Radicava): A novel neuroprotective agent for the treatment of amyotrophic lateral sclerosis. P&T  2018; 43(1): 25-8.
 [PMID: 29290672]

[211]
Watanabe K, Tanaka M, Yuki S, Hirai M, Yamamoto Y. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? J Clin Biochem Nutr  2018; 62(1): 20-38.
 [http://dx.doi.org/10.3164/jcbn.17-62] [PMID: 29371752]

[212]
Abe K, Aoki M, Tsuji S, et al. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: A randomised, double-blind, placebo-controlled trial. Lancet Neurol  2017; 16(7): 505-12.
 [http://dx.doi.org/10.1016/S1474-4422(17)30115-1] [PMID: 28522181]

[213]
Cho H, Shukla S. Role of edaravone as a treatment option for patients with amyotrophic lateral sclerosis. Pharmaceuticals (Basel)  2020; 14(1): 29.
 [http://dx.doi.org/10.3390/ph14010029] [PMID: 33396271]

[214]
Oh Y, Jun HS. Effects of glucagon-like peptide-1 on oxidative stress and Nrf2 signaling. Int J Mol Sci  2017; 19(1): 26.
 [http://dx.doi.org/10.3390/ijms19010026] [PMID: 29271910]

[215]
Pan Y, Li W, Feng Y, Xu J, Cao H. Edaravone attenuates experimental asthma in mice through induction of HO-1 and the Keap1/Nrf2 pathway. Exp Ther Med  2020; 19(2): 1407-16.
 [PMID: 32010316]

[216]
Ahmed SMU, Luo L, Namani A, Wang XJ, Tang X. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis  2017; 1863(2): 585-97.
 [http://dx.doi.org/10.1016/j.bbadis.2016.11.005] [PMID: 27825853]

[217]
Liu J, Jiang Y, Zhang G, Lin Z, Du S. Protective effect of edaravone on blood-brain barrier by affecting NRF-2/HO-1 signaling pathway. Exp Ther Med  2019; 18(4): 2437-42.
 [http://dx.doi.org/10.3892/etm.2019.7859] [PMID: 31555355]

[218]
Liu Z, Yang C, Meng X, Li Z, Lv C, Cao P. Neuroprotection of edaravone on the hippocampus of kainate-induced epilepsy rats through Nrf2/HO-1 pathway. Neurochem Int  2018; 112: 159-65.
 [http://dx.doi.org/10.1016/j.neuint.2017.07.001] [PMID: 28697972]

[219]
Ikeda K, Iwasaki Y. Edaravone, a free radical scavenger, delayed symptomatic and pathological progression of motor neuron disease in the wobbler mouse. PLoS One  2015; 10(10): e0140316.
 [http://dx.doi.org/10.1371/journal.pone.0140316] [PMID: 26469273]

[220]
Cho H, Shukla S. Role of edaravone as a treatment option for patients with amyotrophic lateral sclerosis. Pharmaceuticals  2020; 14(1): 29.
 [http://dx.doi.org/10.3390/ph14010029] [PMID: 33396271]

[221]
Campuzano V, Montermini L, Moltò MD, et al. Friedreich’s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science  1996; 271(5254): 1423-7.
 [http://dx.doi.org/10.1126/science.271.5254.1423] [PMID: 8596916]

[222]
Andermann F. Nicolaus Friedreich and degenerative atrophy of the posterior columns of the spinal cord. Can J Neurol Sci  1976; 3(4): 275-7.
 [http://dx.doi.org/10.1017/S0317167100025452] [PMID: 793699]

[223]
Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet  1983; 321(8334): 1151-5.
 [http://dx.doi.org/10.1016/S0140-6736(83)92879-9] [PMID: 6133167]

[224]
Pandolfo M. Molecular pathogenesis of Friedreich ataxia. Arch Neurol  1999; 56(10): 1201-8.
 [http://dx.doi.org/10.1001/archneur.56.10.1201] [PMID: 10520935]

[225]
Metz G, Coppard N, Cooper JM, et al. Rating disease progression of Friedreich’s ataxia by the International Cooperative Ataxia Rating Scale: Analysis of a 603-patient database. Brain  2013; 136(1): 259-68.
 [http://dx.doi.org/10.1093/brain/aws309] [PMID: 23365101]

[226]
Reetz K, Dogan I, Costa AS, et al. Biological and clinical characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS) cohort: A cross-sectional analysis of baseline data. Lancet Neurol  2015; 14(2): 174-82.
 [http://dx.doi.org/10.1016/S1474-4422(14)70321-7] [PMID: 25566998]

[227]
Chiang S, Kovacevic Z, Sahni S, et al. Frataxin and the molecular mechanism of mitochondrial iron-loading in Friedreich’s ataxia. Clin Sci  2016; 130(11): 853-70.
 [http://dx.doi.org/10.1042/CS20160072] [PMID: 27129098]

[228]
González-Cabo P, Palau F. Mitochondrial pathophysiology in Friedreich’s ataxia. J Neurochem  2013; 126 (Suppl. 1): 53-64.
 [http://dx.doi.org/10.1111/jnc.12303] [PMID: 23859341]

[229]
Dürr A, Cossee M, Agid Y, et al. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med  1996; 335(16): 1169-75.
 [http://dx.doi.org/10.1056/NEJM199610173351601] [PMID: 8815938]

[230]
Harding AE. Friedreich’s ataxia: A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain  1981; 104(3): 589-620.
 [http://dx.doi.org/10.1093/brain/104.3.589] [PMID: 7272714]

[231]
Vankan P. Prevalence gradients of Friedreich’s Ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge. J Neurochem  2013; 126(S1): 11-20.
 [http://dx.doi.org/10.1111/jnc.12215] [PMID: 23859338]

[232]
Bradley JL, Blake JC, Chamberlain S, Thomas PK, Cooper JM, Schapira AH. Clinical, biochemical and molecular genetic correlations in Friedreich’s ataxia. Hum Mol Genet  2000; 9(2): 275-82.
 [http://dx.doi.org/10.1093/hmg/9.2.275] [PMID: 10607838]

[233]
Santos R, Lefevre S, Sliwa D, Seguin A, Camadro JM, Lesuisse E. Friedreich ataxia: Molecular mechanisms, redox considerations, and therapeutic opportunities. Antioxid Redox Signal  2010; 13(5): 651-90.
 [http://dx.doi.org/10.1089/ars.2009.3015] [PMID: 20156111]

[234]
Lodi R, Tonon C, Calabrese V, Schapira AHV. Friedreich’s ataxia: From disease mechanisms to therapeutic interventions. Antioxid Redox Signal  2006; 8(3-4): 438-43.
 [http://dx.doi.org/10.1089/ars.2006.8.438] [PMID: 16677089]

[235]
Boddaert N, Le Quan Sang KH, Rötig A, et al. Selective iron chelation in Friedreich ataxia: Biologic and clinical implications. Blood  2007; 110(1): 401-8.
 [http://dx.doi.org/10.1182/blood-2006-12-065433] [PMID: 17379741]

[236]
Li K, Besse EK, Ha D, Kovtunovych G, Rouault TA. Iron-dependent regulation of frataxin expression: Implications for treatment of Friedreich ataxia. Hum Mol Genet  2008; 17(15): 2265-73.
 [http://dx.doi.org/10.1093/hmg/ddn127] [PMID: 18424449]

[237]
Kakhlon O, Manning H, Breuer W, et al. Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation. Blood  2008; 112(13): 5219-27.
 [http://dx.doi.org/10.1182/blood-2008-06-161919] [PMID: 18796625]

[238]
Goncalves S, Paupe V, Dassa EP, Rustin P. Deferiprone targets aconitase: Implication for Friedreich’s ataxia treatment. BMC Neurol  2008; 8(1): 20.
 [http://dx.doi.org/10.1186/1471-2377-8-20] [PMID: 18558000]

[239]
Schulz JB, Dehmer T, Schöls L, et al. Oxidative stress in patients with Friedreich ataxia. Neurology  2000; 55(11): 1719-21.
 [http://dx.doi.org/10.1212/WNL.55.11.1719] [PMID: 11113228]

[240]
Pandolfo M. Frataxin deficiency and mitochondrial dysfunction. Mitochondrion  2002; 2(1-2): 87-93.
 [http://dx.doi.org/10.1016/S1567-7249(02)00039-9] [PMID: 16120311]

[241]
Rustin P, von Kleist-Retzow JC, Chantrel-Groussard K, Sidi D, Munnich A, Rötig A. Effect of idebenone on cardiomyopathy in Friedreich’s ataxia: A preliminary study. Lancet  1999; 354(9177): 477-9.
 [http://dx.doi.org/10.1016/S0140-6736(99)01341-0] [PMID: 10465173]

[242]
Seznec H, Simon D, Monassier L, et al. Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia. Hum Mol Genet  2004; 13(10): 1017-24.
 [http://dx.doi.org/10.1093/hmg/ddh114] [PMID: 15028670]

[243]
Di Prospero NA, Baker A, Jeffries N, Fischbeck KH. Neurological effects of high-dose idebenone in patients with Friedreich’s ataxia: A randomised, placebo-controlled trial. Lancet Neurol  2007; 6(10): 878-86.
 [http://dx.doi.org/10.1016/S1474-4422(07)70220-X] [PMID: 17826341]

[244]
Lagedrost SJ, Sutton MSJ, Cohen MS, et al. Idebenone in Friedreich ataxia cardiomyopathy—results from a 6-month phase III study (IONIA). Am Heart J  2011; 161(3): 639-645.e1.
 [http://dx.doi.org/10.1016/j.ahj.2010.10.038] [PMID: 21392622]

[245]
Sturm B, Stupphann D, Kaun C, et al. Recombinant human erythropoietin: Effects on frataxin expression in vitro. Eur J Clin Invest  2005; 35(11): 711-7.
 [http://dx.doi.org/10.1111/j.1365-2362.2005.01568.x] [PMID: 16269021]

[246]
Acquaviva F, Castaldo I, Filla A, et al. Recombinant human erythropoietin increases frataxin protein expression without increasing mRNA expression. Cerebellum  2008; 7(3): 360-5.
 [http://dx.doi.org/10.1007/s12311-008-0036-x] [PMID: 18581197]

[247]
Herman D, Jenssen K, Burnett R, Soragni E, Perlman SL, Gottesfeld JM. Histone deacetylase inhibitors reverse gene silencing in Friedreich’s ataxia. Nat Chem Biol  2006; 2(10): 551-8.
 [http://dx.doi.org/10.1038/nchembio815] [PMID: 16921367]

[248]
Rai M, Soragni E, Jenssen K, et al. HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PLoS One  2008; 3(4): e1958.
 [http://dx.doi.org/10.1371/journal.pone.0001958] [PMID: 18463734]

[249]
Behl C, Skutella T, Lezoualc’H F, et al. Neuroprotection against oxidative stress by estrogens: Structure-activity relationship. Mol Pharmacol  1997; 51(4): 535-41.
 [http://dx.doi.org/10.1124/mol.51.4.535] [PMID: 9106616]

[250]
Richardson TE, Yang SH, Wen Y, Simpkins JW. Estrogen protection in Friedreich’s ataxia skin fibroblasts. Endocrinology  2011; 152(7): 2742-9.
 [http://dx.doi.org/10.1210/en.2011-0184] [PMID: 21540287]

[251]
Prokai-Tatrai K, Perjesi P, Rivera-Portalatin NM, Simpkins JW, Prokai L. Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. Steroids  2008; 73(3): 280-8.
 [http://dx.doi.org/10.1016/j.steroids.2007.10.011] [PMID: 18068745]

[252]
Simpkins JW, Yang SH, Sarkar SN, Pearce V. Estrogen actions on mitochondria—Physiological and pathological implications. Mol Cell Endocrinol  2008; 290(1-2): 51-9.
 [http://dx.doi.org/10.1016/j.mce.2008.04.013] [PMID: 18571833]

[253]
Wen Y, Li W, Poteet EC, et al. Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem  2011; 286(18): 16504-15.
 [http://dx.doi.org/10.1074/jbc.M110.208447] [PMID: 21454572]

[254]
Oskoui MB, Darras BT, De Vivo DC. Spinal muscular atrophy: 125 years later and on the verge of a cure. In: Spinal muscular atrophy.  Academic Press 2017; pp. 3-19.

[255]
Sucato DJ. Spine deformity in spinal muscular atrophy. J Bone Joint Surg Am  2007; 89(S1)
 [PMID: 17272431]

[256]
Zerres K, Rudnik-Schöneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci  1997; 146(1): 67-72.
 [http://dx.doi.org/10.1016/S0022-510X(96)00284-5] [PMID: 9077498]

[257]
Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell  1995; 80(1): 155-65.
 [http://dx.doi.org/10.1016/0092-8674(95)90460-3] [PMID: 7813012]

[258]
Roy N, Mahadevan MS, McLean M, et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell  1995; 80(1): 167-78.
 [http://dx.doi.org/10.1016/0092-8674(95)90461-1] [PMID: 7813013]

[259]
Burghes AHM, Beattie CE. Spinal muscular atrophy: Why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci  2009; 10(8): 597-609.
 [http://dx.doi.org/10.1038/nrn2670] [PMID: 19584893]

[260]
Eggert C, Chari A, Laggerbauer B, Fischer U. Spinal muscular atrophy: The RNP connection. Trends Mol Med  2006; 12(3): 113-21.
 [http://dx.doi.org/10.1016/j.molmed.2006.01.005] [PMID: 16473550]

[261]
Chen TH, Chang JG, Yang YH, et al. Randomized, double-blind, placebo-controlled trial of hydroxyurea in spinal muscular atrophy. Neurology  2010; 75(24): 2190-7.
 [http://dx.doi.org/10.1212/WNL.0b013e3182020332] [PMID: 21172842]

[262]
Messina S, Pane M, Sansone V, et al. Expanded access program with Nusinersen in SMA type I in Italy: Strengths and pitfalls of a successful experience. Neuromuscul Disord  2017; 27(12): 1084-6.
 [http://dx.doi.org/10.1016/j.nmd.2017.09.006] [PMID: 29132728]

[263]
Singh NN, Howell MD, Androphy EJ, Singh RN. How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy. Gene Ther  2017; 24(9): 520-6.
 [http://dx.doi.org/10.1038/gt.2017.34] [PMID: 28485722]

[264]
Hua Y, Sahashi K, Hung G, et al. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev  2010; 24(15): 1634-44.
 [http://dx.doi.org/10.1101/gad.1941310] [PMID: 20624852]

[265]
Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of nusinersen (ISIS-SMN Rx) in children with spinal muscular atrophy. Neurology  2016; 86(10): 890-7.
 [http://dx.doi.org/10.1212/WNL.0000000000002445] [PMID: 26865511]

[266]
Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: A phase 2, open-label, dose-escalation study. Lancet  2016; 388(10063): 3017-26.
 [http://dx.doi.org/10.1016/S0140-6736(16)31408-8] [PMID: 27939059]

[267]
Kuntz N, Farwell W, Zhong ZJ, et al. Nusinersen in infants diagnosed with spinal muscular atrophy (SMA): Study design and initial interim efficacy and safety findings from the phase 3 international ENDEAR study (CCI. 002). Neurology  2017; 88(S16)

[268]
Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med  2017; 377(18): 1723-32.
 [http://dx.doi.org/10.1056/NEJMoa1702752] [PMID: 29091570]

[269]
Haché M, Swoboda KJ, Sethna N, et al. Intrathecal injections in children with spinal muscular atrophy: Nusinersen clinical trial experience. J Child Neurol  2016; 31(7): 899-906.
 [http://dx.doi.org/10.1177/0883073815627882] [PMID: 26823478]

[270]
Poirier A, Weetall M, Heinig K, et al. Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs. Pharmacol Res Perspect  2018; 6(6): e00447.
 [http://dx.doi.org/10.1002/prp2.447] [PMID: 30519476]

[271]
Sturm S, Günther A, Jaber B, et al. A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier. Br J Clin Pharmacol  2019; 85(1): 181-93.
 [http://dx.doi.org/10.1111/bcp.13786] [PMID: 30302786]

[272]
Dhillon S. Risdiplam: First Approval. Drugs  2020; 80(17): 1853-8.
 [http://dx.doi.org/10.1007/s40265-020-01410-z] [PMID: 33044711]

[273]
Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol  2009; 27(1): 59-65.
 [http://dx.doi.org/10.1038/nbt.1515] [PMID: 19098898]

[274]
Valori CF, Ning K, Wyles M, et al. Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy. Sci Transl Med  2010; 2(35): 35ra42.
 [http://dx.doi.org/10.1126/scitranslmed.3000830] [PMID: 20538619]

[275]
Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med  2017; 377(18): 1713-22.
 [http://dx.doi.org/10.1056/NEJMoa1706198] [PMID: 29091557]

[276]
Al-Zaidy S, Pickard AS, Kotha K, et al. Health outcomes in spinal muscular atrophy type 1 following AVXSí 101 gene replacement therapy. Pediatr Pulmonol  2019; 54(2): 179-85.
 [http://dx.doi.org/10.1002/ppul.24203] [PMID: 30548438]

[277]
Mendell JR, Lehman KJ, McColly M, et al. AVXS-101 gene-replacement therapy (GRT) in spinal muscular atrophy type 1 (SMA1): Long-term follow-up from the phase 1 clinical trial (S25.006). Neurology  2019; 92(S15)
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DOI https://dx.doi.org/10.2174/1566524023666230907093451	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666
当代分子医药

神经退行性疾病:新的希望和前景

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Molecular and Cellular Mechanisms in Vertigo / Vestibular Disorders

当代分子医药

神经退行性疾病:新的希望和前景

摘要

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