Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin.
Lyons, David A
Semin Cell Dev Biol
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Franklin, R., Frisén, J., & Lyons, D. A. (2021). Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin.. Semin Cell Dev Biol, 116 3-9. https://doi.org/10.1016/j.semcdb.2020.09.009
The biology of CNS remyelination has attracted considerable interest in recent years because of its translational potential to yield regenerative therapies for the treatment of chronic and progressive demyelinating diseases such as multiple sclerosis (MS). Critical to devising myelin regenerative therapies is a detailed understanding of how remyelination occurs. The accepted dogma, based on animal studies, has been that the myelin sheaths of remyelination are made by oligodendrocytes newly generated from adult oligodendrocyte progenitor cells in a classical regenerative process of progenitor migration, proliferation and differentiation. However, recent human and a growing number of animal studies have revealed a second mode of remyelination in which mature oligodendrocytes surviving within an area of demyelination are able to regenerate new myelin sheaths. This discovery, while opening up new opportunities for therapeutic remyelination, has also raised the question of whether there are fundamental differences in myelin regeneration between humans and some of the species in which experimental remyelination studies are conducted. Here we review how this second mode of remyelination can be integrated into a wider and revised framework for understanding remyelination in which apparent species differences can be reconciled but that also raises important questions for future research.
We thank Sarah Neely, University of Edinburgh, for generating the schematic figure. Work in the Franklin lab is supported by UK Multiple Sclerosis Society, the Adelson Medical ResearchFoundation, and a core support grant from the Wellcome and MRC to the Wellcome-MedicalResearch Council Cambridge Stem Cell Institute. , in the Frisen lab by Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, Knutoch Alice Wallenbergs Stiftelse and the ERC, and in the Lyons lab by the Wellcome Trust, the UK Multiple Sclerosis Society, the MRC, and Biogen.
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF) (unknown)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
External DOI: https://doi.org/10.1016/j.semcdb.2020.09.009
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311392
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Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/