TY - JOUR
TI - Cellular senescence and failure of myelin repair in multiple sclerosis
AU - Koutsoudaki, P.N.
AU - Papadopoulos, D.
AU - Passias, P.-G.
AU - Koutsoudaki, P.
AU - Gorgoulis, V.G.
JO - Mechanisms of Ageing and Development
PY - 2020
VL - 192
TODO - null
SP - null
PB - Elsevier Ireland Ltd
SN - 0047-6374
TODO - 10.1016/j.mad.2020.111366
TODO - astragaloside IV;  dasatinib;  ginsenoside;  ginsenoside F1;  ginsenoside Rg 1;  high mobility group B1 protein;  idebenone;  lipofuscin;  metformin;  navitoclax;  opicinumab;  quercetin;  rapamycin;  reactive oxygen metabolite;  sirtuin 1;  transcription factor Sox2;  unclassified drug, Article;  axon;  cell aging;  cell cycle arrest;  cell differentiation;  cell migration;  cell population;  cell proliferation;  cell regeneration;  central nervous system;  disease course;  drug mechanism;  drug targeting;  human;  loss of function mutation;  multiple sclerosis;  nerve conduction;  nerve fiber degeneration;  neuroprotection;  nonhuman;  oligodendrocyte precursor cell;  phenotype;  priority journal;  remyelinization;  aging;  cell aging;  drug development;  drug effect;  metabolism;  molecularly targeted therapy;  multiple sclerosis;  myelin sheath;  pharmacology;  physiology, Aging;  Cellular Senescence;  Drug Discovery;  Humans;  Molecular Targeted Therapy;  Multiple Sclerosis;  Myelin Sheath;  Remyelination;  Sphingosine 1 Phosphate Receptor Modulators
TODO - Remyelination 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. © 2020 The Authors
ER -