阿尔茨海默病（AD）是一类神经退行性疾病，beta淀粉样蛋白（A-beta）是引起神经元细胞死亡并导致AD发生的重要因素之一。本课题组的前期研究结果显示，miRNA-200家族受到A-beta调控，在AD小鼠脑组织中随着AD进程发生动态变化，而PTEN可能是其靶基因之一。此动态变化可能是在A-beta诱导的内质网应激（ERS）调控下发生的。本项目拟在前期工作基础上，以miRNA-200c为其家族成员代表，在细胞和动物模型中，通过过表达或敲减miRNA-200c或PTEN，进一步确定miRNA-200c及其靶基因PTEN在AD发生过程中的作用，并使用ERS抑制剂，明确ERS对miRNA-200c—PTEN的动态调控作用，以及在AD进程中的影响。为前期关于miRNA-200与AD发生发展之间的关系研究找到明确的作用机制，并为AD的发生发展机制提供新的线索和证据。

Alzheimer’s disease (AD) is a kind of neurodegenrative disease. Beta-amyloid (A-beta) is important for neuronal death in AD. In our previous study, we found that the expression level of microRNA-200 (miRNA-200) family could be regulated by A-beta. There was a dynamical expression change of miRNA-200 in AD mice brains along the AD development. In our study, PTEN was found to be one of the potential targets of miRNA-200 family. The dynamical change of miRNA-200 and PTEN might be regulated by A-beta-induced endoplasmic reticulum stress (ERS). In this study, we will use rat or mouse primary cultured neurons as the cell model, PTEN-LoxP conditional knockout mice, PTEN transgeneic mice and APPswe/PS1ΔE9 double transgeneic mice as the mice models. We will overexpress or knock-down miRNA-200c and PTEN in cell and mice model brains to elucidate their roles in AD development. To further understand the regulatory rold of ERS in miRNA-200/PTEN regulation and AD pathologenesis, we will also use ERS inhibitor to study the mechanisms. Based on the above results, we will try to understand the mechanism of ERS-miRNA-200c-PTEN affecting A-beta-related neuronal apoptosis and know more about AD pathogenesis.