{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:21:52Z","timestamp":1790785312204,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ERC Consolidator Grant, AFM-Telethon (EK) and the Association pour la Recherche sur la Scl\u00e9rose Lat\u00e9rale Amyotrophique (ARSLA; MLC and EK).","award":["1"],"award-info":[{"award-number":["1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The \u201cdistal axonopathy\u201d hypothesis in amyotrophic lateral sclerosis (ALS) proposes that pathological changes occur at the neuromuscular junction (NMJ) early in the disease. While acetylcholinesterase (AChE) plays an important role in the functionality of the NMJ, its potential role in ALS remains unexplored. Here, we identified AChE as a limiting factor regulating muscle\/motor neuron connection in a vertebrate model of ALS. Knockdown of the TAR DNA-binding protein 43 (TDP-43) orthologue in zebrafish resulted in early defects of motor functions coupled with NMJ disassembly. We found that a partially depleted tdp-43 caused a decrease of ache expression. Importantly, human AChE overexpression reduced the phenotypic defects in the tdp-43 loss of function model, with amelioration of post- and pre-synaptic deficits at the NMJ. In conclusion, our results provide a better understanding of the role of TDP-43 in the NMJ organization and indicate AChE as a contributing factor in the pathology of ALS. In particular, it may be implicated in the early defects that characterize NMJs in this major neurodegenerative disorder.<\/jats:p>","DOI":"10.3390\/cells10020221","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T11:13:53Z","timestamp":1611314033000},"page":"221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["TDP-43 Regulation of AChE Expression Can Mediate ALS-Like Phenotype in Zebrafish"],"prefix":"10.3390","volume":"10","author":[{"given":"Maria-Letizia","family":"Campanari","sequence":"first","affiliation":[{"name":"Team \u201cTranslational Research for Neuronlogical Diseases\u201d, Institut Imagine Inserm U1163, Universit\u00e9 de Paris; Sorbonne Universit\u00e9, Universit\u00e9 Pierre et Marie Curie (UPMC), Universit\u00e9 de Paris 06, Unit\u00e9 Mixte 75, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 1127, Centre National de la Recherche Scientifique (CNRS) Unit\u00e9 Mixte de Recherche 7225 Institut du Cerveau et de la Moelle \u00c9pini\u00e8re (ICM), 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Marian","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Research for Neuronlogical Diseases\u201d, Institut Imagine Inserm U1163, Universit\u00e9 de Paris; Sorbonne Universit\u00e9, Universit\u00e9 Pierre et Marie Curie (UPMC), Universit\u00e9 de Paris 06, Unit\u00e9 Mixte 75, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 1127, Centre National de la Recherche Scientifique (CNRS) Unit\u00e9 Mixte de Recherche 7225 Institut du Cerveau et de la Moelle \u00c9pini\u00e8re (ICM), 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorana","family":"Ciura","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Research for Neuronlogical Diseases\u201d, Institut Imagine Inserm U1163, Universit\u00e9 de Paris; Sorbonne Universit\u00e9, Universit\u00e9 Pierre et Marie Curie (UPMC), Universit\u00e9 de Paris 06, Unit\u00e9 Mixte 75, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 1127, Centre National de la Recherche Scientifique (CNRS) Unit\u00e9 Mixte de Recherche 7225 Institut du Cerveau et de la Moelle \u00c9pini\u00e8re (ICM), 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4118-251X","authenticated-orcid":false,"given":"Edor","family":"Kabashi","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Research for Neuronlogical Diseases\u201d, Institut Imagine Inserm U1163, Universit\u00e9 de Paris; Sorbonne Universit\u00e9, Universit\u00e9 Pierre et Marie Curie (UPMC), Universit\u00e9 de Paris 06, Unit\u00e9 Mixte 75, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 1127, Centre National de la Recherche Scientifique (CNRS) Unit\u00e9 Mixte de Recherche 7225 Institut du Cerveau et de la Moelle \u00c9pini\u00e8re (ICM), 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: From genes to mechanism","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. 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