项目名称: 基于自噬系统mTOR信号通路探讨扶正祛邪中药小复方干预阿尔茨海默病模型的机制研究
项目编号: No.81503628
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 刘美霞
作者单位: 中国中医科学院西苑医院
项目金额: 18万元
中文摘要: 哺乳动物雷帕霉素靶蛋白( mammalian target of rapamycin,mTOR)信号激活导致自噬溶酶体途径障碍是毒性蛋白Aβ、Tau聚集从而引发阿尔茨海默病(Alzheimer's disease,AD)的关键环节,抑制mTOR信号通路过度激活可诱导自噬从而改善认知功能,因此,从mTOR信号通路诱导的细胞自噬来研究AD,无疑为研究中医药干预AD的作用机制提供了新的靶点和切入点,有可能成为干预AD中药疗效的良好评价体系。本研究在前期预实验结果发现扶正祛邪中药小复方对AD模型Aβ蛋白聚集具有明显抑制作用的基础上,以国内较先进的APP/PS1双转基因小鼠及人APP/PS1双基因转染细胞这两种体内外AD模型为实验平台,结合最新AD研究进展,从mTOR信号通路出发,在分子、细胞及整体水平探讨扶正祛邪中药复方干预AD的可能信号转导机制,为中医药防治AD的机理研究和推广应用提供科学依据。
中文关键词: 阿尔茨海默病;细胞自噬;mTOR信号通路;中药复方;扶正祛邪
英文摘要: The activation of mammalian target of rapamycin(mTOR) signaling leading to obstacles of autophagy-lysosome pathway that is a key to induce acculation of Aβ and Tau protein of Alzheimer's disease(AD).The inhibiting activation of mTOR signaling can induce autophagy and improve cognitive.therefore,the study on autophagy of AD from mTOR signaling pathway could provide a new target and become a good Evaluation system of Traditional Chinese medicine curative effect to AD.The early prediction experiment results showed that the chinese herbal compound of Fuzheng Quxie can inhibt obviously the acculation of Aβ protein,based on which,this study would use APP/PS1 double transgenic mouse as AD model in vivo and APP/PS1 double transgenic cell as AD model in vitro to observe the effect of extracts from chinese herbal compound of Fuzheng Quxie on the mTOR signaling pathway of AD,and provide a new science basis for AD treatment with TCM methods.
英文关键词: Alzheimer's disease;autophagy;mTOR signaling pathway;chinese herbal compound;Fuzheng Quxie