Franklin Robin J M, Bodini Benedetta, Goldman Steven A
Altos Labs Cambridge Institute of Science, Cambridge CB21 6GH, United Kingdom
Sorbonne Université, Paris Brain Institute, CNRS, INSERM, Paris 75013, France.
Cold Spring Harb Perspect Biol. 2024 Mar 1;16(3):a041371. doi: 10.1101/cshperspect.a041371.
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.
长期以来,哺乳动物中枢神经系统(CNS)无法进行自发再生一直被视为神经生物学的核心原则。然而,虽然成年哺乳动物中枢神经系统的神经元成分在很大程度上确实如此,但颗粒神经元的离散群体除外,其神经胶质成分并非如此。特别是,少突胶质细胞的丧失会导致脱髓鞘,引发一种自发且通常高效的再生反应——髓鞘再生,即产生新的少突胶质细胞并将髓鞘恢复到裸露的轴突上。然而,人类的髓鞘再生并非没有局限性,多种脱髓鞘疾病都与持续性和致残性的髓鞘丧失有关。在这项工作中,我们将:(1)回顾髓鞘再生的生物学过程,包括涉及的细胞和信号;(2)描述髓鞘再生何时发生、何时以及为何失败,包括其失败的后果;(3)讨论通过刺激内源性少突胶质细胞祖细胞以及将这些细胞移植到脱髓鞘大脑中,在儿童和成人脱髓鞘疾病中治疗性增强髓鞘再生的方法。