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Review
. 2019 Aug 3;8(8):825.
doi: 10.3390/cells8080825.

The Molecular Basis for Remyelination Failure in Multiple Sclerosis

Joel Gruchot  1 , Vivien Weyers  1 , Peter Göttle  1 , Moritz Förster  1 , Hans-Peter Hartung  1 , Patrick Küry  1 , David Kremer  2
Affiliations
Review

The Molecular Basis for Remyelination Failure in Multiple Sclerosis

Joel Gruchot et al. Cells. .

Abstract

Myelin sheaths in the central nervous system (CNS) insulate axons and thereby allow saltatory nerve conduction, which is a prerequisite for complex brain function. Multiple sclerosis (MS), the most common inflammatory autoimmune disease of the CNS, leads to the destruction of myelin sheaths and the myelin-producing oligodendrocytes, thus leaving behind demyelinated axons prone to injury and degeneration. Clinically, this process manifests itself in significant neurological symptoms and disability. Resident oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) are present in the adult brain, and can differentiate into mature oligodendrocytes which then remyelinate the demyelinated axons. However, for multiple reasons, in MS the regenerative capacity of these cell populations diminishes significantly over time, ultimately leading to neurodegeneration, which currently remains untreatable. In addition, microglial cells, the resident innate immune cells of the CNS, can contribute further to inflammatory and degenerative axonal damage. Here, we review the molecular factors contributing to remyelination failure in MS by inhibiting OPC and NSC differentiation or modulating microglial behavior.

Keywords: microglia; multiple sclerosis; neural stem cells; oligodendroglial precursor cells; remyelination.

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Conflict of interest statement

J.G., V.W. and M.F. have no conflicts of interests. D.K. received compensation for speaking from Grifols SA. P.G. and P.K. performed consultancy work for GeNeuro. P.K. received compensation for speaking from Sanofi Genzyme. H.-P.H. received compensation for consulting, speaking, and serving on steering committees from Bayer Healthcare, Biogen, Celgene Receptos, GeNeuro, MedImmune, Merck, Novartis, Roche, Sanofi Genzyme, and Teva with approval by the rector of Heinrich-Heine-University.

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