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纤毛病:HDAC6 是否代表一个新的治疗靶点?

Ciliopathies: Does HDAC6 Represent a New Therapeutic Target?

机构信息

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.

出版信息

Trends Pharmacol Sci. 2016 Feb;37(2):114-119. doi: 10.1016/j.tips.2015.11.002. Epub 2015 Dec 2.

Abstract

Cilia are cellular appendages with critical roles in sensing and transducing environmental signals and guiding fluid flow. Consistent with these diverse activities, defects in ciliary structure or function have been implicated in a variety of human diseases, collectively known as 'ciliopathies'. Histone deacetylase 6 (HDAC6) is a unique cytoplasmic enzyme that regulates many biological processes through its deacetylase and ubiquitin-binding activities. There is accumulating evidence that HDAC6 is a major driver of ciliary disassembly. Small-molecule compounds that inhibit HDAC6 have been demonstrated to restore ciliary structure and function in several different ciliopathies. Here, we discuss recent findings that highlight the important role for HDAC6 in mediating ciliary disassembly and the potential for HDAC6-selective inhibitors as therapeutics for specific ciliopathies.

摘要

纤毛是具有关键作用的细胞附属物,可用于感知和转导环境信号并引导流体流动。与这些多样化的活动一致,纤毛结构或功能的缺陷与各种人类疾病有关,统称为“纤毛病”。组蛋白去乙酰化酶 6(HDAC6)是一种独特的细胞质酶,通过其去乙酰化酶和泛素结合活性来调节许多生物学过程。越来越多的证据表明,HDAC6 是纤毛解体的主要驱动因素。已证明抑制 HDAC6 的小分子化合物可恢复几种不同纤毛病中的纤毛结构和功能。在这里,我们讨论了最近的发现,这些发现强调了 HDAC6 在介导纤毛解体中的重要作用,以及 HDAC6 选择性抑制剂作为特定纤毛病治疗药物的潜力。

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