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Epigenetic Mechanisms of Ischemic Stroke
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2019-10-01 , DOI: 10.1134/s1990747819040093
A. B. Uzdensky , S. V. Demyanenko

Stroke is one of the main causes of human death and disability. Occlusion of the cerebral vessels in minutes leads to oxygen and glucose depletion and the infarction of nervous tissue. However, neuroprotectors that can rescue neurons have not been found yet. This review describes the biochemical processes leading to cell death in the ischemic brain and the molecular factors that spread the damage to neighboring tissues and form the transition zone (penumbra). Even though ischemic damage generally suppresses biosynthetic processes, some proteins are expressed in the ischemic penumbra. Epigenetic processes are the mechanisms of the global regulation of transcription and protein synthesis as well as the functional state of cells. The review considers main epigenetic processes that regulate gene expression and protein synthesis: DNA methylation, methylation and acetylation of histones. The main attention is paid to epigenetic regulatory proteins: DNA methyltransferases, histone acetyltransferases, histone deacetylases and their isoforms. Their role in the brain responses to ischemic damage is discussed. The inhibition of some epigenetic proteins is one of the promising strategies for the treatment of ischemic stroke. The capabilities of some inhibitors of histone deacetylases and DNA methyltransferases as potential neuroprotectors in ischemic stroke are discussed.

中文翻译:

缺血性中风的表观遗传机制

中风是人类死亡和残疾的主要原因之一。几分钟内脑血管的闭塞会导致氧气和葡萄糖的消耗以及神经组织的梗塞。然而,尚未发现可以拯救神经元的神经保护剂。这篇综述描述了导致缺血脑细胞死亡的生化过程,以及将损伤扩散到邻近组织并形成过渡区(半影)的分子因素。尽管缺血性损伤通常会抑制生物合成过程,但一些蛋白质在缺血半暗带中表达。表观遗传过程是转录和蛋白质合成以及细胞功能状态的全局调节机制。该综述考虑了调节基因表达和蛋白质合成的主要表观遗传过程:DNA 甲基化、组蛋白的甲基化和乙酰化。主要关注表观遗传调控蛋白:DNA 甲基转移酶、组蛋白乙酰转移酶、组蛋白去乙酰化酶及其同种型。讨论了它们在脑对缺血性损伤反应中的作用。抑制某些表观遗传蛋白是治疗缺血性中风的有前景的策略之一。讨论了一些组蛋白去乙酰化酶和 DNA 甲基转移酶抑制剂作为缺血性中风潜在神经保护剂的能力。抑制某些表观遗传蛋白是治疗缺血性中风的有前景的策略之一。讨论了一些组蛋白去乙酰化酶和 DNA 甲基转移酶抑制剂作为缺血性中风潜在神经保护剂的能力。抑制某些表观遗传蛋白是治疗缺血性中风的有前景的策略之一。讨论了一些组蛋白去乙酰化酶和 DNA 甲基转移酶抑制剂作为缺血性中风潜在神经保护剂的能力。
更新日期:2019-10-01
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