Intracellular signaling pathway regulation of myelination and remyelination in the CNS

JM Gaesser, SL Fyffe-Maricich - Experimental neurology, 2016 - Elsevier
JM Gaesser, SL Fyffe-Maricich
Experimental neurology, 2016Elsevier
The restoration of myelin sheaths on demyelinated axons remains a major obstacle in the
treatment of multiple sclerosis (MS). Currently approved therapies work by modulating the
immune system to reduce the number and rate of lesion formation but are only partially
effective since they are not able to restore lost myelin. In the healthy CNS, myelin continues
to be generated throughout life and spontaneous remyelination occurs readily in response
to insults. In patients with MS, however, remyelination eventually fails, at least in part as a …
Abstract
The restoration of myelin sheaths on demyelinated axons remains a major obstacle in the treatment of multiple sclerosis (MS). Currently approved therapies work by modulating the immune system to reduce the number and rate of lesion formation but are only partially effective since they are not able to restore lost myelin. In the healthy CNS, myelin continues to be generated throughout life and spontaneous remyelination occurs readily in response to insults. In patients with MS, however, remyelination eventually fails, at least in part as a result of a failure of oligodendrocyte precursor cell (OPC) differentiation and the subsequent production of new myelin. A better understanding of the molecular mechanisms and signaling pathways that drive the process of myelin sheath formation is therefore important in order to speed the development of novel therapeutics designed to target remyelination. Here we review data supporting critical roles for three highly conserved intracellular signaling pathways: Wnt/β-catenin, PI3K/AKT/mTOR, and ERK/MAPK in the regulation of OPC differentiation and myelination both during development and in remyelination. Potential points of crosstalk between the three pathways and important areas for future research are also discussed.
Elsevier