Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
Eur J Neurosci. 2019 Jun;49(11):1371-1387. doi: 10.1111/ejn.14337. Epub 2019 Jan 30.
Myelin is lipid-rich structure that is necessary to avoid leakage of electric signals and to ensure saltatory impulse conduction along axons. Oligodendrocytes in central nervous system (CNS) and Schwann cells in peripheral nervous system (PNS) are responsible for myelin formation. Axonal demyelination after injury or diseases greatly impairs normal nervous system function. Therefore, understanding how the myelination process is programmed, coordinated, and maintained is crucial for developing therapeutic strategies for remyelination in the nervous system. Epigenetic mechanisms have been recognized as a fundamental contributor in this process. In recent years, histone modification, DNA modification, ATP-dependent chromatin remodeling, and non-coding RNA modulation are very active area of investigation. We will present a conceptual framework that integrates crucial epigenetic mechanisms with the regulation of oligodendrocyte and Schwann cell lineage progression during development and myelin degeneration in pathological conditions. It is anticipated that a refined understanding of the molecular basis of myelination will aid in the development of treatment strategies for debilitating disorders that involve demyelination, such as multiple sclerosis in the CNS and neuropathies in the PNS.
髓鞘是富含脂质的结构，对于避免电信号泄漏和确保轴突上的跳跃式冲动传导是必需的。中枢神经系统（CNS）中的少突胶质细胞和周围神经系统（PNS）中的施万细胞负责髓鞘形成。损伤或疾病后的轴突脱髓鞘极大地损害了正常的神经系统功能。因此，了解髓鞘形成过程是如何被编程、协调和维持的，对于开发神经系统中的髓鞘再生治疗策略至关重要。表观遗传机制已被认为是这一过程的一个基本贡献者。近年来，组蛋白修饰、DNA 修饰、ATP 依赖性染色质重塑和非编码 RNA 调节是非常活跃的研究领域。我们将提出一个概念框架，将关键的表观遗传机制与发育过程中少突胶质细胞和施万细胞谱系进展的调节以及病理条件下髓鞘变性的调节结合起来。预计对髓鞘形成的分子基础的更深入理解将有助于开发治疗涉及脱髓鞘的衰弱性疾病的策略，如中枢神经系统的多发性硬化症和周围神经系统的神经病变。
