Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro, Italy.
School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, U.K.
Curr Pharm Des. 2017;23(37):5546-5562. doi: 10.2174/1381612823666171024130001.
Emerging evidence suggests that epigenetic mechanisms are involved in different brain functions such as the development of the nervous system and normal neuronal function. At the same time, it has been proposed that several neurological diseases are in part, caused by aberrant epigenetic modifications. Nevertheless, the mechanisms underlying pathological alterations in the brain genome are not completely understood.
Post-transcriptional histone acetylation is a major mechanism of chromatin remodeling, contributing to epigenetic regulation of gene transcription. Histone deacetylases (HDACs) are a family of proteins involved in both physiological and pathological conditions by regulating the status of chromatin histone acetylation. It is now becoming clear that epigenetic regulatory mechanisms may also play a major role in epilepsy; modulation of chromatin structure through histone modifications has emerged as an important regulator of gene transcription in the brain and altered histone acetylation seems to contribute to changes in gene expression associated with epilepsy and the epileptogenic process. Histone modification is crucial for regulating neurobiological processes such as neural network function, synaptic plasticity, and synaptogenesis which also contribute to the pathophysiology of epilepsy.
The role of epigenetics in epilepsy development is a new and emerging research area; the present article reviews the recent findings on the role played by HDACs and the possible function of different histone modifications in epilepsy and epileptogenesis. Inhibitors of HDACs (HDACIs) have been tested in different experimental models of epilepsy with some success. We also review the results from these studies, which indicate HDACIs as potential new therapeutic agents for the treatment of human epilepsy.
新出现的证据表明，表观遗传机制参与了不同的大脑功能，如神经系统的发育和正常神经元功能。同时，有人提出，几种神经疾病部分是由异常的表观遗传修饰引起的。然而，大脑基因组中病理改变的机制尚不完全清楚。
转录后组蛋白乙酰化是染色质重塑的主要机制，有助于基因转录的表观遗传调控。组蛋白去乙酰化酶（HDACs）是一类在生理和病理条件下都参与的蛋白质，通过调节染色质组蛋白乙酰化的状态来调节。现在越来越清楚的是，表观遗传调控机制也可能在癫痫中起主要作用；通过组蛋白修饰来调节染色质结构已成为大脑中基因转录的重要调节剂，而组蛋白乙酰化的改变似乎与癫痫和致痫过程中与基因表达相关的变化有关。组蛋白修饰对于调节神经生物学过程至关重要，如神经网络功能、突触可塑性和突触发生，这些过程也有助于癫痫的病理生理学。
表观遗传学在癫痫发展中的作用是一个新的和新兴的研究领域；本文综述了 HDACs 所起作用的最新发现以及不同组蛋白修饰在癫痫和致痫中的可能功能。HDAC 抑制剂（HDACIs）已在不同的癫痫实验模型中进行了测试，并取得了一定的成功。我们还回顾了这些研究的结果，表明 HDACIs 可能是治疗人类癫痫的潜在新治疗药物。
