Yang Shuang-Shuang, Zhang Rui, Wang Gang, Zhang Yong-Fang
Department of Pharmacology, Institute of Medical Sciences, School of Medicine, Shanghai Jiao Tong University, 280 South Chongqing Road, Shanghai, 200025 China.
Department of Neurology Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Ruijin 2nd Road 197, Shanghai, 200025 China.
Transl Neurodegener. 2017 Jul 10;6:19. doi: 10.1186/s40035-017-0089-1. eCollection 2017.
Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is associated with learning and memory impairment in the elderly. Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen. In a number of recent studies, inhibitors of histone deacetylase (HDACs) have been found to be a novel promising therapeutic agents for neurological disorders, particularly for AD and other neurodegenerative diseases. Although HDAC inhibitors have the ability to ameliorate cognitive impairment, successful treatments in the classic AD animal model are rarely translated into clinical trials. As for the reduction of unwanted side effects, the development of HDAC inhibitors with increased isoform selectivity or seeking other directions is a key issue that needs to be addressed. The review focused on literatures on epigenetic mechanisms in recent years, especially on histone acetylation in terms of the enhancement of specificity, efficacy and avoiding side effects for treating AD.
阿尔茨海默病(AD)是一种慢性神经退行性疾病,与老年人的学习和记忆障碍有关。最近的研究发现,通过组蛋白乙酰化进行染色质重塑来治疗AD是一种有前景的治疗方案。在最近的一些研究中,组蛋白去乙酰化酶(HDACs)抑制剂已被发现是治疗神经系统疾病,特别是AD和其他神经退行性疾病的一种新型有前景的治疗药物。尽管HDAC抑制剂有改善认知障碍的能力,但在经典AD动物模型中的成功治疗很少转化为临床试验。至于减少不良副作用,开发具有更高亚型选择性的HDAC抑制剂或寻求其他方向是一个需要解决的关键问题。这篇综述聚焦于近年来关于表观遗传机制的文献,特别是在增强治疗AD的特异性、疗效和避免副作用方面的组蛋白乙酰化。