项目名称: MicroRNA-146a调控Rho激酶信号通路对阿尔茨海默病免疫炎性机制影响的实验研究
项目编号: No.81200842
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 神经系统疾病、精神疾病
项目作者: 任汝静
作者单位: 上海交通大学
项目金额: 23万元
中文摘要: miRNA-146a作为miRNA家族的重要成员之一,可能通过调控关键信号蛋白-Rho激酶1(ROCK1)及相关通路,进而调控炎性因子因子的分泌、炎性细胞的募集以及突触功能,参与了阿尔茨海默病(Alzheimer's disease,AD)的免疫炎性机制。本研究拟在我们前期工作的基础上,针对miRNA-146a调控ROCK信号通路在AD免疫炎性机制中的作用,以稳定转染miR-146a的N2a及BV2细胞及APP/PS1双转基因小鼠模型为工具,以miRNA-146a调控ROCK1参与炎性机制为切入点,研究miRNA-146a与ROCK1的关系以及在AD免疫炎性机制中的作用及相关通路;同时并对miRNA-146a作为新型生物标记物、ROCK1作为新的治疗靶点进行研究。本研究将进一步阐明AD的炎性发病机制,并寻找新的治疗靶点,为新型药物的开发奠定坚实的基础。
中文关键词: 微RNA;阿尔茨海默病;Rho蛋白激酶;;
英文摘要: As one of most important members of micorRNA family, miRNA-146a involved in the inflammatory mechanism for Alzheimer's disease(AD) through modulation of Rho Kinase(ROCK) signaling pathway, and subsequent regultions of cytokine/chemokine secreting, recruitment of macrophage, and synaptic functions. Based on our previous evidences, we will carry out the experimental study of modulation of ROCK signaling pathway in response to MicroRNA-146a in inflammatory mechanism for AD. In cellular models (N2a and BV2 cell lines with stable expression of miRNA-146a) and transgenic animal models (APP/PS1 mice), the study will focus on the intercations between miRNA-146a and ROCK1, and the associated signaling pathway in inflammatory mechanism for AD. Meanwhile, we will investigate the possiblity for miRNA-146a as biomarkers and ROCK1 as novel therapeutic target, respectively. Notably, the study will promote to clarifications of the inflammatory mechanism, identifying novel therapeutic target and seeking new drugs for AD.
英文关键词: microRNA;Alzheimer’s disease;Rho-associated protein kinase;;