title: Lithium down-regulates histone deacetylase 1 (HDAC1) and induces degradation of mutant huntingtin.
abstract: Lithium is an effective mood stabilizer that has been clinically used to treat bipolar disorder for several decades. Recent studies have suggested that lithium possesses robust neuroprotective and anti-tumor properties. Thus far, a large number of lithium targets have been discovered. Here, we report for the first time that HDAC1 is a target of lithium. Lithium significantly down-regulated HDAC1 at the translational level by targeting HDAC1 mRNA. We also showed that depletion of HDAC1 is essential for the neuroprotective effects of lithium and for the lithium-mediated degradation of mutant huntingtin through the autophagic pathway. Our studies explain the multiple functions of lithium and reveal a novel mechanism for the function of lithium in neurodegeneration.
authors.affiliation: From the State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wu
authors.forename: Shui-Di
authors.initials: SD
authors.lastname: Zheng
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Huang
authors.forename: Li-Chong
authors.initials: LC
authors.lastname: Yan
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Yin
authors.forename: Hai-Neng
authors.initials: HN
authors.lastname: Xu
authors.forename: Kang-Jian
authors.initials: KJ
authors.lastname: Zhang
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Gui
authors.forename: Liang
authors.initials: L
authors.lastname: Chu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Liu
mesh_terms: D001343:Autophagy; D000067879:CELF1 Protein; D015536:Down-Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D000071058:Huntingtin Protein; D008094:Lithium / Q000494:pharmacology*; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D000067879:CELF1 Protein; C102843:CELF1 protein, human; C086055:HTT protein, human; D056572:Histone Deacetylase Inhibitors; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
keywords: Autophagy; Cell Biology; Cell Signaling; Histone Deacetylase; Histone Deacetylase Inhibitors; Huntington Disease; MicroRNA; Neurodegeneration