期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 49, 页码 35500-35510出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.479865
关键词
Cell Biology; Cell Signaling; Histone Deacetylase; Histone Deacetylase Inhibitors; Huntington Disease; Neurodegeneration; MicroRNA; Autophagy
资金
- National Nature Science Foundation of China [30623003]
- National Basic Research Program of China (973 Program) [2010CB529901]
- National Science and Technology Specific Project of Hepatitis and Hepatoma Related Program [2008ZX10002-023]
- National Basic Research Committee of Science and Technology [06ZR14072, 074119508]
Background: Lithium and valproic acid (VPA) exhibit a robust neuroprotective and anti-tumor effects in neural cells and tumor cells. Results: Lithium significantly down-regulates HDAC1 at the translational level by targeting HDAC1 mRNA. Conclusion: The decrease in HDAC1 is essential for the lithium-mediated, autophagic degradation of mutant huntingtin. Significance: This report is the first demonstration that HDAC1 decreases in response to lithium treatment. 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.
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