Hu Zhiping, Zhong Bingwu, Tan Jieqiong, Chen Chunli, Lei Qiang, Zeng Liuwang
Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Department of Traditional Chinese Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Mol Neurobiol. 2017 Apr;54(3):1887-1905. doi: 10.1007/s12035-016-9788-3. Epub 2016 Feb 19.
Despite great progresses in the treatment and prevention of ischemic stroke, it is still among the leading causes of death and serious long-term disability all over the world, indicating that innovative neural regenerative and neuroprotective agents are urgently needed for the development of therapeutic approaches with greater efficacy for ischemic stroke. More and more evidence suggests that a spectrum of epigenetic processes play an important role in the pathophysiology of cerebral ischemia. In the present review, we first discuss recent developments in epigenetic mechanisms, especially their roles in the pathophysiology of cerebral ischemia. Specifically, we focus on DNA methylation, histone deacetylase, histone methylation, and microRNAs (miRNAs) in the regulation of vascular and neuronal regeneration after cerebral ischemia. Additionally, we highlight epigenetic strategies for ischemic stroke treatments, including the inhibition of histone deacetylase enzyme and DNA methyltransferase activities, and miRNAs. These therapeutic strategies are far from clinic use, but preliminary data indicate that neuroprotective agents targeting these pathways can modulate neural cell regeneration and promote brain repair and functional recovery after cerebral ischemia. A better understanding of how epigenetics influences the process and progress of cerebral ischemia will pave the way for discovering more sensitive and specific biomarkers and new targets and therapeutics for ischemic stroke.
尽管在缺血性中风的治疗和预防方面取得了巨大进展，但它仍然是全球主要的死亡原因和严重长期残疾的原因之一，这表明迫切需要创新的神经再生和神经保护药物来开发对缺血性中风更有效的治疗方法。越来越多的证据表明，一系列表观遗传过程在脑缺血的病理生理学中起重要作用。在本综述中，我们首先讨论表观遗传机制的最新进展，特别是它们在脑缺血病理生理学中的作用。具体而言，我们关注DNA甲基化、组蛋白去乙酰化酶、组蛋白甲基化和微小RNA（miRNA）在脑缺血后血管和神经元再生调节中的作用。此外，我们强调缺血性中风治疗的表观遗传策略，包括抑制组蛋白去乙酰化酶和DNA甲基转移酶活性以及miRNA。这些治疗策略距离临床应用还很远，但初步数据表明，针对这些途径的神经保护药物可以调节神经细胞再生，并促进脑缺血后的脑修复和功能恢复。更好地理解表观遗传学如何影响脑缺血的过程和进展将为发现更敏感和特异的生物标志物以及缺血性中风的新靶点和治疗方法铺平道路。
