{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:21:19Z","timestamp":1790425279433,"version":"4.1.0"},"reference-count":177,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006510","name":"Association pour la Recherche sur la Scl\u00e9rose Lat\u00e9rale Amyotrophique et autres Maladies du Motoneurone","doi-asserted-by":"publisher","award":["RAK19097LLP"],"award-info":[{"award-number":["RAK19097LLP"]}],"id":[{"id":"10.13039\/501100006510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Motor neurons and their axons reaching the skeletal muscle have long been considered as the best characterized targets of the degenerative process observed in amyotrophic lateral sclerosis (ALS). However, the involvement of glial cells was also more recently reported. Although oligodendrocytes have been underestimated for a longer time than other cells, they are presently considered as critically involved in axonal injury and also conversely constitute a target for the toxic effects of the degenerative neurons. In the present review, we highlight the recent advances regarding oligodendroglial cell involvement in the pathogenesis of ALS. First, we present the oligodendroglial cells, the process of myelination, and the tight relationship between axons and myelin. The histological abnormalities observed in ALS and animal models of the disease are described, including myelin defects and oligodendroglial accumulation of pathological protein aggregates. Then, we present data that establish the existence of dysfunctional and degenerating oligodendroglial cells, the chain of events resulting in oligodendrocyte degeneration, and the most recent molecular mechanisms supporting oligodendrocyte death and dysfunction. Finally, we review the arguments in support of the primary versus secondary involvement of oligodendrocytes in the disease and discuss the therapeutic perspectives related to oligodendrocyte implication in ALS pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms22073426","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T13:17:53Z","timestamp":1616764673000},"page":"3426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Defective Oligodendroglial Lineage and Demyelination in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Elisabeth","family":"Traiffort","sequence":"first","affiliation":[{"name":"Diseases and Hormones of the Nervous System U1195 INSERM, Paris Saclay University, 80 Rue du G\u00e9n\u00e9ral Leclerc, 94276 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9930-7824","authenticated-orcid":false,"given":"S\u00e9verine","family":"Morisset-Lopez","sequence":"additional","affiliation":[{"name":"Centre de Biophysique Mol\u00e9culaire, UPR 4301 CNRS, Orl\u00e9ans University, INSERM, rue Charles Sadron, CEDEX 02, 45071 Orleans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Moussaed","sequence":"additional","affiliation":[{"name":"Centre de Biophysique Mol\u00e9culaire, UPR 4301 CNRS, Orl\u00e9ans University, INSERM, rue Charles Sadron, CEDEX 02, 45071 Orleans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Zahaf","sequence":"additional","affiliation":[{"name":"Diseases and Hormones of the Nervous System U1195 INSERM, Paris Saclay University, 80 Rue du G\u00e9n\u00e9ral Leclerc, 94276 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1080\/21646821.2015.1075181","article-title":"Amyotrophic Lateral Sclerosis (ALS) and Related Motor Neuron Diseases: An Overview","volume":"55","author":"Morris","year":"2015","journal-title":"Neurodiagn. 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