本项目以延缓阿尔茨海默症（AD）发生、发展为研究背景，应用生物无机化学、细胞无机化学以及分子生物学等多学科的方法与理论，采用基因工程大量表达硒蛋白突变体、再通过化学修饰将蛋白链中丝氨酸残基变成硒代半胱氨酸这一新思路，制备硒蛋白及其模拟蛋白。研究内容包括1) 基因工程制备硒蛋白及其突变体; 2) 用化学方法对硒蛋白的突变体进行修饰,将丝氨酸残基变成硒代半胱氨酸; 3) 用生物无机化学方法研究其构效关系; 4) 用细胞无机化学方法研究不同硒蛋白及其模拟物对AD相关细胞的作用以及AD相关指标的变化和分子机理，开展细胞的蛋白质组及金属组学研究；5）用生物信息学方法预测硒蛋白及其模拟物的结构与功能。本项目将为阐明硒和硒蛋白延缓AD发生、发展的分子机制提供基础数据。

This project is going to study the effect and mechanism of selenoproteins and their mimics on delaying the onset and development of Alzheimer's disease (AD), using multiple methods and theories in bioinorganic chemistry, cellular inorganic chemistry, and molecular biology. A great quantity of selenoproteins and their mimics will be prepared based on a new route that the mutants of selenoproteins will be over-expressed firstly by genetic engineering, and the serine residue(s) in those proteins will then be modified into selenocysteine(s) by chemical reactions. Five parts will be included in this project: 1) preparation of selenoproteins and their mutants by genetic engineering; 2) modification of the serine residue(s) to selenocysteine(s) by chemical reactions; 3) protein structure-functional study by the methods of bioinorganic chemistry; 4) effect and mechanism of different selenoproteins and their mimics on AD relevant cells and AD pathological features, including the proteomics and metallomics study of those treated cells; 5) prediction of the structure and function of those selenoprotein mimics through bioinformatics. This project will provide elementary data for elucidating the molecular mechanism of selenium and selenoproteins in preventing Alzheimer's disease.