Roslyn and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, New York, NY, USA.
Transl Stroke Res. 2011 Mar 1;2(1):7-16. doi: 10.1007/s12975-010-0051-3.
The recent explosion of interest in epigenetics and chromatin biology has made a significant impact on our understanding of the pathophysiology of cerebral ischemia and led to the identification of new treatment strategies for stroke, such as those that employ histone deacetylase inhibitors. These are key advances; however, the rapid pace of discovery in chromatin biology and innovation in the development of chromatin-modifying agents implies there are emerging classes of drugs that may also have potential benefits in stroke. Herein, we discuss how various chromatin regulatory factors and their recently identified inhibitors may serve as drug targets and therapeutic agents for stroke, respectively. These factors primarily include members of the repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor macromolecular complex, polycomb group (PcG) proteins, and associated chromatin remodeling factors, which have been linked to the pathophysiology of cerebral ischemia. Further, we suggest that, because of the key roles played by REST, PcG proteins and other chromatin remodeling factors in neural stem and progenitor cell (NSPC) biology, chromatin-modifying agents can be utilized not only to mitigate ischemic injury directly but also potentially to promote endogenous NSPC-mediated brain repair mechanisms.
近年来，人们对表观遗传学和染色质生物学的兴趣激增，这极大地促进了我们对脑缺血病理生理学的理解，并为中风的治疗策略（如使用组蛋白去乙酰化酶抑制剂）提供了新的思路。这些是重要的进展；然而，染色质生物学的快速发现和染色质修饰剂的创新发展意味着，可能还有其他类别的药物在中风治疗方面具有潜在的益处。本文讨论了各种染色质调节因子及其最近发现的抑制剂如何分别作为中风的药物靶点和治疗药物。这些因子主要包括抑制元件-1沉默转录因子 (REST)/神经元抑制因子的成员、多梳组 (PcG) 蛋白及其相关的染色质重塑因子，它们与脑缺血的病理生理学有关。此外，我们认为，由于 REST、PcG 蛋白和其他染色质重塑因子在神经干细胞和祖细胞 (NSPC) 生物学中的关键作用，染色质修饰剂不仅可以直接减轻缺血性损伤，还可能促进内源性 NSPC 介导的脑修复机制。
