Cellular senescence and failure of myelin repair in multiple sclerosis
AffiliationMolecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens
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AbstractRemyelination is a physiological response to demyelinating events aiming to restore saltatory conduction and preserve axonal integrity. Resident oligodendrocyte precursor cells (OPC) of the CNS tissue under appropriate conditions are mobilized to proliferate, migrate, and differentiate, in order to produce new myelin sheaths in the demyelinated lesion. In multiple sclerosis (MS), the most common immune-mediated demyelinating disease, remyelination efficiency declines with increasing age and disease duration. As myelin regeneration attempts in clinical trials so far are scarce, and have been met with limited success, the need to explore new remyelinating strategies is more compelling. Recently, ageing and cellular senescence have been implicated in the pathophysiology of a number of neurodegenerative diseases, including multiple sclerosis. Evidence on OPC senescence brings forward the possibility of exploiting cellular senescence as a possible target for promoting the endogenous remyelinating capacity of the CNS. Here we discuss the data indicating how cellular senescence affects remyelination, and the putative benefits to be drawn through the use of senolytic or senomorphic therapies targeting senescent cell populations in MS.
CitationKoutsoudaki PN, Papadopoulos D, Passias PG, Koutsoudaki P, Gorgoulis VG. Cellular senescence and failure of myelin repair in multiple sclerosis. Mech Ageing Dev. 2020;192:111366.
JournalMechanisms of Ageing and Development
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