Breaking the barriers to remyelination in multiple sclerosis.
Journal
Current opinion in pharmacology
ISSN: 1471-4973
Titre abrégé: Curr Opin Pharmacol
Pays: England
ID NLM: 100966133
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
26
11
2021
revised:
19
01
2022
accepted:
25
01
2022
pubmed:
8
3
2022
medline:
12
4
2022
entrez:
7
3
2022
Statut:
ppublish
Résumé
Chronically demyelinated axons are rendered susceptible to degeneration through loss of trophic support from oligodendrocytes and myelin, and this process underlies disability progression in multiple sclerosis. Promoting remyelination is a promising neuroprotective therapeutic strategy, but to date, has not been achieved through simply promoting oligodendrocyte precursor cell differentiation, and it is clear that a detailed understanding of the molecular mechanisms underlying failed remyelination is required to guide future therapeutic approaches. In multiple sclerosis, remyelination is impaired by extrinsic inhibitory cues in the lesion microenvironment including secreted effector molecules released from compartmentalized immune cells and reactive glia, as well as by intrinsic defects in oligodendrocyte lineage cells, most notably increased metabolic demands causing oxidative stress and accelerated cellular senescence. Promising advances in our understanding of the cellular and molecular mechanisms underlying these processes offers hope for strategically designed interventions to facilitate remyelination thereby resulting in robust clinical benefits.
Identifiants
pubmed: 35255453
pii: S1471-4892(22)00020-0
doi: 10.1016/j.coph.2022.102194
pmc: PMC8995341
mid: NIHMS1778538
pii:
doi:
Types de publication
Journal Article
Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102194Subventions
Organisme : NINDS NIH HHS
ID : R01 NS041435
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement PAC is PI on grants to JHU from Principia and Genentech, and has received personal compensation for consulting from Biogen, Avidea, and Disarm Therapeutics. MG and RB have no conflicts.
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