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脑卒中的表观遗传学机制和潜在治疗靶点。

Epigenetic mechanisms and potential therapeutic targets in stroke.

机构信息

Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI, USA.

Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.

出版信息

J Cereb Blood Flow Metab. 2022 Nov;42(11):2000-2016. doi: 10.1177/0271678X221116192. Epub 2022 Jul 19.

Abstract

Accumulating evidence indicates a central role for epigenetic modifications in the progression of stroke pathology. These epigenetic mechanisms are involved in complex and dynamic processes that modulate post-stroke gene expression, cellular injury response, motor function, and cognitive ability. Despite decades of research, stroke continues to be classified as a leading cause of death and disability worldwide with limited clinical interventions. Thus, technological advances in the field of epigenetics may provide innovative targets to develop new stroke therapies. This review presents the evidence on the impact of epigenomic readers, writers, and erasers in both ischemic and hemorrhagic stroke pathophysiology. We specifically explore the role of DNA methylation, DNA hydroxymethylation, histone modifications, and epigenomic regulation by long non-coding RNAs in modulating gene expression and functional outcome after stroke. Furthermore, we highlight promising pharmacological approaches and biomarkers in relation to epigenetics for translational therapeutic applications.

摘要

越来越多的证据表明,表观遗传修饰在中风病理的进展中起着核心作用。这些表观遗传机制参与了复杂而动态的过程,调节中风后的基因表达、细胞损伤反应、运动功能和认知能力。尽管经过了几十年的研究,中风仍然是全球范围内导致死亡和残疾的主要原因之一,而临床干预手段有限。因此,表观遗传学领域的技术进步可能为开发新的中风治疗方法提供创新靶点。这篇综述介绍了表观基因组读码器、写码器和擦除器在缺血性和出血性中风病理生理学中的作用的证据。我们特别探讨了 DNA 甲基化、DNA 羟甲基化、组蛋白修饰以及长非编码 RNA 的表观遗传调控在调节中风后基因表达和功能结果中的作用。此外,我们强调了与表观遗传学相关的有前景的药物治疗方法和生物标志物,以实现转化治疗应用。

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