朊蛋白在阿尔茨海默病视网膜病变的生物学功能及分子机制研究

项目名称： 朊蛋白在阿尔茨海默病视网膜病变的生物学功能及分子机制研究

项目编号： No.81460092

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 周琼

作者单位： 南昌大学

项目金额： 49万元

中文摘要： 阿尔茨海默病（AD）是一种常见致死性神经退行性疾病。我们前期及最近研究发现正常和AD鼠视网膜神经节细胞(RGCs) 有朊蛋白（PrPc）表达，并可通过结合PrPc受体激活AKT及NFκB信号传导通道参与细胞凋亡。因此，我们推测PrPc可能依赖RGCs中EGFR-NF-κB及Insulin-AKT信号转导通路调控AD RGCs。我们拟通过PrPc-shRNA调控PrPc表达，观察和分析沉默和过表达PrPc在AD RGCs生物学功能变化；探讨PrPc抗体在AD鼠、KO鼠、AD/KO杂合鼠活体内和体外培养RGCs中的作用，深入了解AKT及NF-κB信号传导通路在其中发挥的作用及机制，尝试揭示AD视网膜发病的分子机制，分析朊蛋白在AD视网膜退行性病变中所起的作用及可能的调控机制，为AD的早期诊断及治疗靶点提供新的思路和依据。

中文关键词： 朊蛋白；β-淀粉样蛋白；阿尔茨海默病；视网膜神经节细胞；分子机制

英文摘要： Alzheimer disease (AD) is a common fatal neurodegenerative diseases. Our previous and recent studies found that prion protein (PrPc) has been found to be expressed in the retinal ganglion cells (RGCs) in normal and AD model rats and recently detected to induce cell apoptosis through AKT and NFκB singaling pathway in other tissues. Therefore, we speculated that whether PrPc could regulate AD RGCs apoptosis through inactivating Insulin-AKT and EGFR-NFκB signaling pathways. In this project, we will study the expression of PrPc in retina, and elucidate the biological function of PrPc in AD RGCs through modulating the expression of PrPc in cell and animal model. PrPc silence in AD mice , KO mice and AD/KO heterozygous mice will be performed to further confirm that PrPc induces AD RGCs apoptosis. We will examine the inhibit role of PrPc antibody in AD RGCs apoptosis induced by AKT and NFκB singaling pathway in vitro and in vivo.We expect to reveal the role and mechanism of PrPc-mediated AD RGCs apoptosis, and provide a new therapy compound for early treatment of AD induced retinopathy.

英文关键词： PrPc;amyloid β-protein;Alzheimer disease;RGCs;Molecular Mechanism