药学学报, 2021, 56(1): 29-36
姚开云, 丁虹琬, 曹琳玉, 高银阁, 张建军, 王贵彬. 组蛋白去乙酰化酶抑制剂的抗抑郁前景[J]. 药学学报, 2021, 56(1): 29-36.
YAO Kai-yun, DING Hong-wan, CAO Lin-yu, GAO Yin-ge, ZHANG Jian-jun, WANG Gui-bin. Prospects for histone deacetylase inhibitors as antidepressants[J]. Acta Pharmaceutica Sinica, 2021, 56(1): 29-36.

姚开云, 丁虹琬, 曹琳玉, 高银阁, 张建军, 王贵彬
中国医学科学院、北京协和医学院药物研究所, 新药作用机制研究和药效评价北京市重点实验室, 北京 100050
抑郁症是一种发病率较高的严重精神疾病,目前对其病理机制尚未全面了解,临床治疗效果十分有限。最近的研究表明,发生在大脑特定脑区的表观遗传调控——即不改变脱氧核糖核酸(deoxyribonucleic acid,DNA)编码的情况下调节基因活性,可能是环境因素与个体遗传相互作用以影响抑郁症发病风险的关键机制。因此,靶向表观遗传调控的药物可能成为开发抗抑郁药的新方向。组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitors,HDACi)是一类具有抑制组蛋白去乙酰化酶(histone deacetylase,HDAC)活性的化合物。本文从HDAC与抑郁症的关系入手,集中讨论了在临床前研究中具有抗抑郁药效的HDACi,及其治疗抑郁症的潜在机制与主要局限性,并对未来研究进行了展望和讨论。
关键词:    组蛋白去乙酰化酶抑制剂      抑郁症      表观遗传学      乙酰化作用     
Prospects for histone deacetylase inhibitors as antidepressants
YAO Kai-yun, DING Hong-wan, CAO Lin-yu, GAO Yin-ge, ZHANG Jian-jun, WANG Gui-bin
Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Depression is a serious mental illness with a high incidence. At present, we do not fully understand the specific pathological mechanisms of depression, and the efficacy of drug treatments is very limited. Recent studies have shown that epigenetic changes that occur in specific brain regions may be a key mechanism by which environmental factors to interact with individuals to influence the risk of depression. Therefore, drugs that target epigenetic regulation may become a new direction for the development of antidepressants. Histone deacetylase inhibitors (HDACi) are a class of compounds that inhibit histone deacetylase activity, which has been reported to be associated with depression; this article addresses the use of HDACi in preclinical studies, and their potential therapeutic role and limitations of use in depression.
Key words:    histone deacetylase inhibitor    depression    epigenomics    acetylation   
收稿日期: 2020-07-20
DOI: 10.16438/j.0513-4870.2020-1217
基金项目: 国家重点研发资助项目(2017YFC0803608);国家重大新药创制专项(2018ZX09711001-003-001);国家自然科学基金面上项目(81471355).
通讯作者: 王贵彬,Tel:86-10-63165190,Fax:86-10-63182192,E-mail:guibinwang@imm.ac.cn
Email: guibinwang@imm.ac.cn
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