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      Intracellular Signaling Pathway Regulation of Myelination and Remyelination in the CNS

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          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.

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          Author and article information

          Journal
          0370712
          3660
          Exp Neurol
          Exp. Neurol.
          Experimental neurology
          0014-4886
          1090-2430
          17 March 2016
          5 March 2016
          September 2016
          01 September 2017
          : 283
          : Pt B
          : 501-511
          Affiliations
          Department of Pediatrics, Division of Neurology, University of Pittsburgh, Pittsburgh, PA, 15224
          Author notes
          [* ]Correspondence to: Sharyl L. Fyffe-Maricich ( sharyl.fyffemaricich@ 123456chp.edu ) University of Pittsburgh, One Children’s Hospital Dr., 4401 Penn Ave., RRB Rm 3512, Pittsburgh, PA, 15224, ph 412-692-6400
          Article
          PMC5010983 PMC5010983 5010983 nihpa768292
          10.1016/j.expneurol.2016.03.008
          5010983
          26957369
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