a-synuclein DNA甲基化在帕金森病发病机制中的作用及肉苁蓉总苷干预实验研究

项目名称： a-synuclein DNA甲基化在帕金森病发病机制中的作用及肉苁蓉总苷干预实验研究

项目编号： No.81202814

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 赵卿

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 帕金森病(PD)是一种复杂神经退行性疾病，发病率逐年升高，且无根本治愈方法。我们认为基因和环境相互作用是导致PD发病重要环节，从表观遗传调控主要方式DNA甲基化角度探讨PD发病机制并开发相关药物可能会取得重要突破。我们前期研究发现PD关键致病基因α-synuclein在神经毒剂诱导PD体内外模型中表达增加，中药提取物GCs对其有神经保护作用，能抑制该基因表达上调。我们运用分子生物学和表观遗传学方法，分别从体内外两个水平检测PD模型α-synuclein蛋白和基因表达水平、DNA甲基化程度和表型三者变化规律和相关性，通过对主要的DNA甲基化转移酶(DNMTs)蛋白、基因表达和酶活性检测探讨α-synuclein DNA甲基化修饰影响PD发病的机制。为进一步开发治疗PD的天然药物，我们还研究了GCs对PD模型神经保护作用与对其α-synuclein DNA甲基化调节之间的关系及相关机制。

中文关键词： a-突触核蛋白；DNA甲基化；肉苁蓉总苷；神经保护；帕金森病

英文摘要： Parkinson's disease (PD) is one of the complex neurodegenerative diseases with increased incidence year by year which lacks fundamental cure. We suppose that the interaction of genetic and environmental factors involved in the pathogenesis of PD and there may be a breakthrough to research mechanism of PD from the view of DNA methylation as one of important forms of epigenetics regulation and develop related drugs. Our previous study found that there were significant increases in gene and protein expressions of α-synuclein in PD model induced by nerve agents in vivo and in vitro.Glycosides of Cistanche (GCs), an extract of Chinese herbal medicine has neuroprotective effects and inhibits expressions of α-synuclein. Firstly applying the theories and methods of epigenetics and molecular biology we investigate the variation and relevance among the gene and protein expressions, DNA methylation of α-synuclein and phenotypes in vivo and in vitro model of PD. Furthermore we study how DNA methylation of α-synuclein affects the pathogenesis of PD through detection on expression of the DNA methyltransferase(DNMTs) and its enzyme activity. At last, for the purpose of developing natural medicine for treatment of PD, we will verify the neuroprotective effect of GCs in the models of PD and observe its effects and explore possib

英文关键词： a-synuclein；DNA methylation；Glycosides of Cistanche(GCs)；neuroprotective；Parkinson’s disease