组蛋白去乙酰化酶6选择性抑制剂的研究进展

Selective histone deacetylase 6 inhibitors: research advances

组蛋白去乙酰化酶6(HDAC6)是Ⅱb类HDAC家族的重要成员,它具有2个去乙酰化结构功能域,并具有独特的生理功能。除参与组蛋白修饰外,HDAC6还靶向包括α-微管蛋白和热休克蛋白90(HSP90)在内的特定底物,并参与蛋白质运输和降解,细胞形态和迁移。HDAC6的失调与许多疾病有关,如癌症、自身免疫性疾病和神经退行性疾病。选择性HDAC6抑制剂因对正常细胞基本无毒性而逐渐成为研究热点,目前已有报道多种类型选择性HDAC6抑制剂。本文综述HDAC6蛋白的结构与功能、HDAC6选择性抑制剂的研究进展和潜在适应证。

The histone deacetylase6(HDAC6)is an important member of the classⅡb HDAC family,which has two deacetylated structural domains and unique physiological functions.In addition to its involvement in histone modifications,HDAC6 also targets specific substrates,includingα-tubulin and heat shock protein 90(HSP90),and is involved in the protein trafficking and degradation as well as the cell morphology and migration.The dysregulation of HDAC6 is associated with many diseases,including cancer,autoimmune and neurodegenerative diseases.Selective HDAC6 inhibitors have become a research hotspot because of their non-toxicity to the normal cells.Several types of selective HDAC6 inhibitors have been reported so far.This review summarizes the protein structure and function of HDAC6 as well as the research progress and potential indications of the selective HDAC6 inhibitors.