硒预防阿尔茨海默症中硒蛋白的新分子机制及关联性

项目名称： 硒预防阿尔茨海默症中硒蛋白的新分子机制及关联性

项目编号： No.31470804

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 刘琼

作者单位： 深圳大学

项目金额： 85万元

中文摘要： 中国60岁以上老人预计到2050年达4.38亿，阿尔茨海默症（AD）患者目前在老人中占1.6%，提示AD可能将给中国社会带来巨大问题。AD发病过程长、呈链锁放大效应，尽早实施干预对预防和治疗AD至关重要。生物微量元素硒缺乏会造成认知功能降低。我们前期研究发现：硒代蛋氨酸能显著改善AD小鼠认知障碍、降低tau蛋白磷酸化、抑制神经突触蛋白减少，提示应对硒预防AD的效果和机制进行全面系统研究。本项目拟采用AD细胞系、原代神经细胞和三转基因AD小鼠，从分子、细胞、动物三个层面，结合实验室已具备的F-肌动蛋白细胞骨架成像和线粒体延时成像技术、各种组学研究手段和生物信息学方法、鼠脑PET活体检测手段，研究不同形态和剂量的含硒物质干预AD病理过程的效果，研究SelR和SelP对AD作用的新机制、多种硒蛋白经TrxR和Trx系统协同参与硒干预AD病理过程的机制。为开发抗AD含硒药物提供理论依据和基础数据。

中文关键词： 硒；硒蛋白；阿尔茨海默病；氧化应激；神经细胞

英文摘要： A recent survey demonstrates that the population of elder people in China (> 60 years) will reach 438 million in 2050. Currently the prevalence of Alzheimer's disease (AD) is 1.6% in elderly, indicating that AD will be a huge problem in China in the future. The cause of AD occurs long before the obviously clinical symptom, and it grows in chain-reaction during the pathological process. Thus, it is very important to prevent the disease in its early stage. Deficiency of selenium, one of the biological trace elements, can result in the decrease of cognitive function. In our previous work, selenomethionine was found to significantly improve cognitive deficit, reduce the level of total tau and phosphorylated tau, mitigate the decrease of synaptic proteins in the hippocampus and cortex of the triple transgenic AD mice. Those results prompt us to systematically study the effect and mechanism of selenium in the prevention of AD. This project will use AD cell lines, primarily cultured neurons, and the triple transgenic AD mice as the study models. Various selenium-containing substances will be investigated for the efficiency in AD prevention at molecular, cellular, and animal levels, with the adoption of advanced methods currently used in our lab, such as the imaging of F-actin cytoskeleton and time-lapse imaging of mitochondria, methods of proteomics, genomics, and bioinformatics, and PET detection of alive mice brain. Meanwhile, new mechanisms of SelR and SelP involved in the pathological process of AD will also be studied, together with the coordination of TrxR and other selenoproteins in the intervention of AD with selenium. This project will provide theoretical support and basic data for the development of new selenium-containing anti-AD drug.

英文关键词： selenium;selenoprotein;Alzheimer's disease;oxidative stress;neuron