解析高脂食物对阿尔茨海默症果蝇的影响及其脂质代谢相关的作用机制

项目名称： 解析高脂食物对阿尔茨海默症果蝇的影响及其脂质代谢相关的作用机制

项目编号： No.31500958

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生理学与整合生物学

项目作者： 项延会

作者单位： 中国科学院遗传与发育生物学研究所

项目金额： 20万元

中文摘要： 阿茨海默症是老年人中多发的一种神经退行性的疾病，它主要临床症状是记忆力衰退，运动行为障碍。近年来虽然有许多关于阿尔茨海默症的报道出现，但是它的发病机理却并不清楚。脂类是大脑行使正常功能的关键调节因子，越来越多的证据表明脂类和包括阿茨海默症在内的许多神经退行性疾病相关。脂质组学是大规模定性和定量研究脂类并了解它们在不同生理病理条件下的功能和变化的方法学。利用脂质组学的方法我们确认了阿尔茨海默症果蝇模型是从脂代谢角度研究阿尔茨海默症的可行的动物模型。通过用不同浓度的椰子油食物处理阿尔茨海默症果蝇，我们看到高脂食物确实加剧了阿尔茨海默症果蝇的病理进程。本课题利用脂质组学方法在果蝇中解析高脂食物对阿茨海默症的影响，通过分析阿茨海默症果蝇的全脂图谱，找出与阿茨海默症相关的脂代谢通路，并结合体内的基因敲减及过表达实验和生化实验进行验证，从而为人类阿茨海默症的预防及机理的探究提供依据。

中文关键词： 高脂食物；阿尔茨海默症；脂质组学；脂质代谢；果蝇

英文摘要： Alzheimer’s disease is a neurodegeneration disease characterized clinically by progressively memory loss and behavior defect, which in the majority of cases occurs late of the life. The pathogenesis of Alzheimer’s disease is still not clear up to now. Lipids are the key regulation factors for normal function in brain. More and more evidences show there is a tight correlation between lipid and neurodegeneration disease like Alzheimer’s disease. For lipid analysis, lipidomics is a high throughput method to measure the quality and quantity of lipid and discover their changes and functions under different physiology or pathology conditions. Here we used lipidomic analysis and confirmed that the Alzheimer’s disease model is a creditable model for dissecting the pathogensis mechanism on lipid metabolism aspect. And we also showed that high fat diet exacerbated the pathogenesis of Alzheimer’s disease. We want to further to dissect the mechanism that how high fat diet affects Alzheimer’s disease in Drosophila. Though the data analysis of the full lipid profiles of Alzheimer’s disease on normal food and high fat diet, we want to find the lipid(s) which correlated to Alzheimer’s disease. We will verify the information we get from lipidomic analysis using genetic and biochemistry approaches. We will knock down (out) or overexpress the lipid(s) related enzyme(s) to see whether the phenotype of Alzheimer’s disease is affected. After that we will get the clue which lipid pathways involved into Alzheimer’s disease and provide more evidences to the prevention and mechanism investigation of Alzheimer’s disease.

英文关键词： high fat diet;Alzheimer's disease;lipidomics;lipid metabolism;Drosophila