Review

Regenerating CNS myelin — from mechanisms to experimental medicines

  • Nature Reviews Neuroscience 18, 753769 (2017)
  • doi:10.1038/nrn.2017.136
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Abstract

Although the core concept of remyelination — based on the activation, migration, proliferation and differentiation of CNS progenitors — has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination.

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Author information

Affiliations

  1. Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AH, UK.

    • Robin J. M. Franklin
  2. MRC Centre for Regenerative Medicine, Edinburgh bioQuarter, University of Edinburgh, Edinburgh, EH16 4UU, UK.

    • Charles ffrench-Constant

Authors

  1. Search for Robin J. M. Franklin in:

  2. Search for Charles ffrench-Constant in:

Contributions

Both authors researched the data for the article, provided a substantial contribution to discussion of content, wrote the article and reviewed and edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Robin J. M. Franklin or Charles ffrench-Constant.

Glossary

Oligodendrocytes

The cells that make myelin in the CNS. A single oligodendrocyte can make up to 80 separate myelin sheaths, although approximately 10–20 is more usual.

Remyelination

The regenerative process involving the generation of new oligodendrocytes from CNS-resident progenitor cells and the formation of new myelin sheaths around the demyelinated axon.

Multiple sclerosis

(MS). A common autoimmune-mediated disease of the CNS that is characterized by multiple acute inflammatory foci involving immune-mediated demyelination that can undergo spontaneous remyelination; with disease progression, this remyelination becomes less efficient, leaving axons chronically demyelinated and prone to irreversible degeneration.

Demyelination

The pathological process in which myelin sheaths are lost from axons that remain intact. It is sometimes called primary demyelination to distinguish it from loss of myelin that is secondary to axonal loss, which is more accurately called Wallerian degeneration and should not be called demyelination.

Schwann cells

The cells that make myelin in the peripheral nervous system. A single Schwann cell only ever makes a single myelin sheath. In certain circumstances, Schwann cells can remyelinate demyelinated axons in the CNS.

g ratio

The ratio of the axon diameter to the diameter of the myelinated axon; this term is used to provide a quantitative measure of the myelin sheath thickness compared with the axon diameter. In remyelination, the g ratio usually increases.

Leucodystrophies

A family of genetic diseases usually characterized by inadequate myelination or demyelination.