中国药理学通报2011，Vol.27Issue(3)：308-311,4.
α-synuclein过表达下调Nurr1转录活性的机制研究
Mechanism of decreased transcriptional activity of Nurr1 induced by α-synuclein over-expression
摘要
Abstract
Aim To study whether α-synuclein would influence transcriptional activity of nuclear receptor related factor 1 ( Nurrl ) in dopaminergic cells and relative mechanism for further understanding the role of αsynuclein in the mechanism of Parkinson ' s disease.Methods Dual luciferase activity assay method and Western blot assay were used to examine the impact of a-synuclein over-expression on transcriptional activity and expression level of Nurrl in PC12 cells respectively; meanwhile expression levels of key signaling molecules in Nurrl regulatory pathway CSK3β/β-catenin were also examined.Results Experiment results showed that α-synuclein over-expression significantly decreased transcriptional activity of Nurrl in PC12 cells ( P ＜ 0.01 ), however, it had no significant effects on the expression level of Nurrl compared with control group.Meanwhile , α-synuclein over-expression significantly decreased GSK3 β ( Ser9 ) phosphorylation level and β-catenin expression level.Conclusioris αsynuclein has a negative effect on the transcriptional activity of Nurrl potentially via regulating GSK3β/βcatenin pathway.关键词
α-synuclein/帕金森病/核受体相关因子-1(Nurr1)/GSK3β/β-catenin/转录活性/PC12细胞分类
医药卫生引用本文复制引用
赵明,苑玉和,金金,孙建栋,陈乃宏..α-synuclein过表达下调Nurr1转录活性的机制研究[J].中国药理学通报,2011,27(3):308-311,4.基金项目
国家自然科学基金资助项目(No 3097887,81073078,81073130,重点项目U832008和90713045) （No 3097887,81073078,81073130,重点项目U832008和90713045）
国家重点科技专项(No 2008ZX09101,2009ZX09303-003) （No 2008ZX09101,2009ZX09303-003）
"重大新药创制"科技重大专项(No 2009ZX09303,2009ZX09301-003-11-1) （No 2009ZX09303,2009ZX09301-003-11-1）
国家教育部博士点基金(No 20070023075,20070023037) （No 20070023075,20070023037）
