Cao Dan-Feng, Zhou Xin-Yu, Guo Qian, Xiang Ming-Yao, Bao Mei-Hua, He Bin-Sheng, Mao Xiao-Yuan
Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha, 410219, China.
Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, China.
Biomark Res. 2024 Nov 19;12(1):142. doi: 10.1186/s40364-024-00687-6.
Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators responsible for gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There are also substantial evidences supporting that aberrant expressions and/activities of HDAC isoforms are reported in epilepsy and HDAC inhibitors (HDACi) have been successfully utilized for therapeutic purposes in this condition. However, the specific mechanisms underlying the role of HDACs in epileptic progression have not been fully understood. Herein, we reviewed the basic information of HDACs, summarized the recent findings associated with the roles of diverse HDAC subunits in epilepsy and discussed the potential regulatory mechanisms by which HDACs affected the development of epilepsy. Additionally, we also provided a brief discussion on the potential of HDACs as promising therapeutic targets for epilepsy treatment, serving as a valuable reference for basic study and clinical translation in epilepsy field.
癫痫仍然是一种常见的慢性神经系统疾病，其特征是神经元异常、反复和超同步放电，给医疗保健系统带来了巨大挑战。尽管几种治疗干预措施已成功用于治疗癫痫，但它们只能缓解症状，无法发挥疾病修饰作用。因此，迫切需要探索其他潜在机制，以开发一种新方法来延缓癫痫进展。大约30年前以来，组蛋白去乙酰化酶（HDACs）作为一种多功能表观遗传调节因子，通过结合组蛋白或非组蛋白底物来负责基因转录，在药物发现中引起了相当大的关注。也有大量证据支持在癫痫中报道了HDAC亚型的异常表达和/或活性，并且HDAC抑制剂（HDACi）已成功用于这种情况下的治疗目的。然而，HDACs在癫痫进展中作用的具体机制尚未完全了解。在此，我们回顾了HDACs的基本信息，总结了与不同HDAC亚基在癫痫中的作用相关的最新发现，并讨论了HDACs影响癫痫发展的潜在调节机制。此外，我们还简要讨论了HDACs作为癫痫治疗有前景的治疗靶点的潜力，为癫痫领域的基础研究和临床转化提供有价值的参考。
