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Lithium Down-regulates Histone Deacetylase 1 (HDAC1) and Induces Degradation of Mutant Huntingtin |
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| Authors: | Shuai Wu Shui-Di Zheng Hong-Ling Huang Li-Chong Yan Xiao-Fei Yin Hai-Neng Xu Kang-Jian Zhang Jing-Hua Gui Liang Chu Xin-Yuan Liu |
| 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 ;§College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 10018, China |
| 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. |
| Keywords: | Cell Biology Cell Signaling Histone Deacetylase Histone Deacetylase Inhibitors Huntington Disease Neurodegeneration MicroRNA Autophagy |