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References
Wen X, An P, Li H, Zhou Z, Sun Y, Wang J. Tau accumulation via reduced autophagy mediates GGGGCC repeat expansion-induced neurodegeneration in Drosophila model of ALS. Neurosci Bull 2020, 36: 1414–1428.
Petrov D, Mansfield C, Moussy A, Hermine O. ALS clinical trials review: 20 years of failure. Are we any closer to registering a new treatment? Front Aging Neurosci 2017, 9: 68.
Ling JP, Pletnikova O, Troncoso JC, Wong PC. TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD. Science 2015, 349: 650–655.
Ma XR, Prudencio M, Koike Y, Vatsavayai SC, Kim G, Harbinski F, et al. TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A. Nature 2022, 603: 124–130.
Brown AL, Wilkins OG, Keuss MJ, Hill SE, Zanovello M, Lee WC, et al. TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A. Nature 2022, 603: 131–137.
van Es MA, Veldink JH, Saris CGJ, Blauw HM, van Vught PWJ, Birve A, et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat Genet 2009, 41: 1083–1087.
Chiò A, Mora G, Restagno G, Brunetti M, Ossola I, Barberis M, et al. UNC13A influences survival in Italian amyotrophic lateral sclerosis patients: A population-based study. Neurobiol Aging 2013, 34: 357.e1-357.e5.
Quade B, Camacho M, Zhao X, Orlando M, Trimbuch T, Xu J, et al. Membrane bridging by Munc13-1 is crucial for neurotransmitter release. eLife 2019, 8: e42806.
Böhme MA, Beis C, Reddy-Alla S, Reynolds E, Mampell MM, Grasskamp AT, et al. Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel–vesicle coupling. Nat Neurosci 2016, 19: 1311–1320.
Varoqueaux F, Sons MS, Plomp JJ, Brose N. Aberrant morphology and residual transmitter release at the Munc13-deficient mouse neuromuscular synapse. Mol Cell Biol 2005, 25: 5973–5984.
Vérièpe J, Fossouo L, Parker JA. Neurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neurons. Nat Commun 2015, 6: 7319.
Matsuo M. Antisense oligonucleotide-mediated exon-skipping therapies: Precision medicine spreading from Duchenne muscular dystrophy. JMA J 2021, 4: 232–240.
Roberts TC, Langer R, Wood MJA. Advances in oligonucleotide drug delivery. Nat Rev Drug Discov 2020, 19: 673–694.
Choi E, Koo T. CRISPR technologies for the treatment of Duchenne muscular dystrophy. Mol Ther 2021, 29: 3179–3191.
McDonald CM, Campbell C, Torricelli RE, Finkel RS, Flanigan KM, Goemans N, et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017, 390: 1489–1498.
Kim G, Gautier O, Tassoni-Tsuchida E, Ma XR, Gitler AD. ALS genetics: Gains, losses, and implications for future therapies. Neuron 2020, 108: 822–842.
Wu LS, Cheng WC, Chen CY, Wu MC, Wang YC, Tseng YH, et al. Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons. Acta Neuropathol Commun 2019, 7: 50.
Yang C, Qiao T, Yu J, Wang H, Guo Y, Salameh J, et al. Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice. PLoS One 2022, 17: e0255710.
Klim JR, Williams LA, Limone F, Guerra San Juan I, Davis-Dusenbery BN, Mordes DA, et al. ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. Nat Neurosci 2019, 22: 167–179.
Melamed Z, López-Erauskin J, Baughn MW, Ouyang Z, Drenner K, Sun Y, et al. Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration. Nat Neurosci 2019, 22: 180–190.
Fiesel FC, Weber SS, Supper J, Zell A, Kahle PJ. TDP-43 regulates global translational yield by splicing of exon junction complex component SKAR. Nucleic Acids Res 2012, 40: 2668–2682.
Shiga A, Ishihara T, Miyashita A, Kuwabara M, Kato T, Watanabe N, et al. Alteration of POLDIP3 splicing associated with loss of function of TDP-43 in tissues affected with ALS. PLoS One 2012, 7: e43120.
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Chen, X., Chu, H. & Dong, Y. UNC13A Gene Brings New Hope for ALS Disease-Modifying Drugs. Neurosci. Bull. 38, 1431–1434 (2022). https://doi.org/10.1007/s12264-022-00924-8
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DOI: https://doi.org/10.1007/s12264-022-00924-8