Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
10
11
2021
accepted:
17
05
2023
medline:
7
7
2023
pubmed:
30
6
2023
entrez:
29
6
2023
Statut:
ppublish
Résumé
Axonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure of denuded axons to immune-mediated damage. Therefore, myelin is widely considered to be a protective structure for axons in multiple sclerosis. Myelinated axons also depend on oligodendrocytes, which provide metabolic and structural support to the axonal compartment. Given that axonal pathology in multiple sclerosis is already visible at early disease stages, before overt demyelination, we reasoned that autoimmune inflammation may disrupt oligodendroglial support mechanisms and hence primarily affect axons insulated by myelin. Here, we studied axonal pathology as a function of myelination in human multiple sclerosis and mouse models of autoimmune encephalomyelitis with genetically altered myelination. We demonstrate that myelin ensheathment itself becomes detrimental for axonal survival and increases the risk of axons degenerating in an autoimmune environment. This challenges the view of myelin as a solely protective structure and suggests that axonal dependence on oligodendroglial support can become fatal when myelin is under inflammatory attack.
Identifiants
pubmed: 37386131
doi: 10.1038/s41593-023-01366-9
pii: 10.1038/s41593-023-01366-9
pmc: PMC10322724
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1218-1228Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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