Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Semin Cell Dev Biol. 2020 Jan;97:74-83. doi: 10.1016/j.semcdb.2019.07.009. Epub 2019 Aug 30.
The repair and functional recovery of the nervous system is a highly regulated process that requires the coordination of many different components including the proper myelination of regenerated axons. Dysmyelination and remyelination failures after injury result in defective nerve conduction, impairing normal nervous system functions. There are many convergent regulatory networks and signaling mechanisms between development and regeneration. For instance, the regulatory mechanisms required for oligodendrocyte lineage progression could potentially play fundamental roles in myelin repair. In recent years, epigenetic chromatin modifications have been implicated in CNS myelination and functional nerve restoration. The pro-regenerative transcriptional program is likely silenced or repressed in adult neural cells including neurons and myelinating cells in the central and peripheral nervous systems limiting the capacity for repair after injury. In this review, we will discuss the roles of epigenetic mechanisms, including histone modifications, chromatin remodeling, and DNA methylation, in the maintenance and establishment of the myelination program during normal oligodendrocyte development and regeneration. We also discuss how these epigenetic processes impact myelination and axonal regeneration, and facilitate the improvement of current preclinical therapeutics for functional nerve regeneration in neurodegenerative disorders or after injury.
神经系统的修复和功能恢复是一个高度调控的过程，需要许多不同成分的协调，包括再生轴突的适当髓鞘形成。损伤后出现的脱髓鞘和髓鞘再生失败会导致神经传导缺陷，从而损害正常的神经系统功能。发育和再生之间存在许多趋同的调控网络和信号机制。例如，少突胶质细胞谱系进展所需的调控机制可能在髓鞘修复中发挥重要作用。近年来，表观遗传染色质修饰与中枢神经系统髓鞘形成和功能神经恢复有关。在成年神经细胞（包括中枢和周围神经系统中的神经元和髓鞘形成细胞）中，可能沉默或抑制促再生转录程序，限制损伤后的修复能力。在这篇综述中，我们将讨论表观遗传机制（包括组蛋白修饰、染色质重塑和 DNA 甲基化）在正常少突胶质细胞发育和再生过程中维持和建立髓鞘形成程序中的作用。我们还讨论了这些表观遗传过程如何影响髓鞘形成和轴突再生，并促进改善神经退行性疾病或损伤后功能神经再生的当前临床前治疗方法。
