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REVIEWS
OligodendrocyteThe myelin-forming cell of the CNS.
*Department of Veterinary Medicine and Cambridge Centre for Brain Repair, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK.
MRC Centre for Regenerative Medicine and MS Society/ University of Edinburgh Centre for Translational Research, Centre for Inflammation Research, The Queens Medical Research Institute, 47 Little France Crescent, Edinburgh,
EH16 4TJ, UK.e-mails: mailto:[email protected]
Web End [email protected] ; mailto:[email protected]
Web End [email protected] doi:10.1038/nrn2480
Demyelination is the pathological process in which myelin sheaths are lost from around axons (Fig.1). In the
CNS demyelination is usually the consequence of a direct insult targeted at the oligodendrocyte, the cell that makes and maintains the myelin sheath. This type of demyelination is sometimes referred to as primary demyelination to distinguish it from secondary demyelin ation (or Wallerian degeneration), in which myelin degenerates as a consequence of primary axonal loss.
From a clinical perspective there are two major causes of primary demyelination in the CNS: genetic abnormalities that affect glia (leukodystrophies), and inflammatory damage to myelin and oligodendrocytes (with multiple sclerosis (MS) being by far the most significant of these inflammatory diseases) (BOX 1). Regardless of its cause, demyelination impairs function: the acute loss of a myelin internode is associated with conduction block. This block can be resolved by redistributing and inserting Na+ channels along the denuded axolemma, to allow nonsaltatory conduction along the demyelinated segment1. In addition to this adaptive response, and in striking contrast to the generally inadequate attempts at regeneration that follow damage to neuronal elements, the sequela to CNS demyelination is often the robust regenerative process of remyelination. In this article we review current know ledge of the biology of remyelination, including the cells and molecular signals that are involved. We also describe when remyelination occurs, when and why it
fails and the consequences of its failure. Lastly we discuss approaches by which it might be enhanced therapeutically in demyelin ating diseases. For other recent reviews that consider some of these issues, see REFS 24.
What is remyelination?
Remyelination is the process in which entire myelin sheaths are restored to demyelinated axons, reinstating saltatory conduction5 and resolving functional deficits6,7
(Fig. 1). The term myelin repair is also sometimes used; however, this term evokes thoughts of a damaged but otherwise intact myelin...