title: Ciliopathies: Does HDAC6 Represent a New Therapeutic Target?
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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ran
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: junzhou@nankai.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002923:Cilia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D058990:Molecular Targeted Therapy; D012120:Respiration Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D056572:Histone Deacetylase Inhibitors; C433811:HDAC6 protein, human; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: HDAC6; HDAC6 inhibitor; ciliary disassembly; ciliopathy; cilium