Robin J.M. Franklin1, Benedetta Bodini2,3 and Steven A. Goldman4,5 1Altos Labs Cambridge Institute of Science, Cambridge CB21 6GH, United Kingdom 2Sorbonne Université, Paris Brain Institute, CNRS, INSERM, Paris 75013, France 3Saint-Antoine Hospital, APHP, Paris 75012, France 4Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA 5University of Copenhagen Faculty of Medicine, Copenhagen 2200, Denmark Correspondence: rfranklinaltoslabs.com

The inability of the mammalian central nervous system (CNS) to undergo spontaneous regeneration has long been regarded as a central tenet of neurobiology. However, while this is largely true of the neuronal elements of the adult mammalian CNS, save for discrete populations of granule neurons, the same is not true of its glial elements. In particular, the loss of oligodendrocytes, which results in demyelination, triggers a spontaneous and often highly efficient regenerative response, remyelination, in which new oligodendrocytes are generated and myelin sheaths are restored to denuded axons. Yet remyelination in humans is not without limitation, and a variety of demyelinating conditions are associated with sustained and disabling myelin loss. In this work, we will (1) review the biology of remyelination, including the cells and signals involved; (2) describe when remyelination occurs and when and why it fails, including the consequences of its failure; and (3) discuss approaches for therapeutically enhancing remyelination in demyelinating diseases of both children and adults, both by stimulating endogenous oligodendrocyte progenitor cells and by transplanting these cells into demyelinated brain.