Department of Physiology, National University of Singapore, Singapore, 117593, Singapore.
Department of Physiology, National University of Singapore, Singapore, 117593, Singapore; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore; National Neuroscience Institute, Singapore, 308433, Singapore.
Free Radic Biol Med. 2021 Jul;170:116-130. doi: 10.1016/j.freeradbiomed.2021.02.030. Epub 2021 Mar 6.
The neural stem cells (NSCs) are essential for normal brain development and homeostasis. The cell state (i.e. quiescent versus activated) and fate (i.e. the cell lineage of choice upon differentiation) of NSCs are tightly controlled by various redox and epigenetic regulatory mechanisms. There is an increasing appreciation that redox and epigenetic regulations are intimately linked, but how this redox-epigenetics crosstalk affects NSC activity remains poorly understood. Another unresolved topic is whether the NSCs actually contribute to brain ageing and neurodegenerative diseases. In this review, we aim to 1) distill concepts that underlie redox and epigenetic regulation of NSC state and fate; 2) provide examples of the redox-epigenetics crosstalk in NSC biology; and 3) highlight potential redox- and epigenetic-based therapeutic opportunities to rescue NSC dysfunctions in ageing and neurodegenerative diseases.
神经干细胞（NSCs）对于正常的大脑发育和稳态至关重要。NSCs 的细胞状态（即静止或激活）和命运（即分化时的首选细胞谱系）受到各种氧化还原和表观遗传调控机制的严格控制。越来越多的人认识到氧化还原和表观遗传调控是密切相关的，但这种氧化还原-表观遗传相互作用如何影响 NSCs 的活性还知之甚少。另一个尚未解决的问题是 NSCs 是否实际上参与了大脑衰老和神经退行性疾病。在这篇综述中，我们旨在：1）提炼出氧化还原和表观遗传调控 NSCs 状态和命运的基本概念；2）提供 NSC 生物学中氧化还原-表观遗传相互作用的实例；3）强调潜在的氧化还原和基于表观遗传的治疗机会，以挽救衰老和神经退行性疾病中 NSCs 的功能障碍。
