硒蛋白R与凝集素的相互作用及其干预阿尔茨海默症的机制

项目名称： 硒蛋白R与凝集素的相互作用及其干预阿尔茨海默症的机制

项目编号： No.31500624

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 陈平

作者单位： 南阳理工学院

项目金额： 20万元

中文摘要： 硒蛋白（SelR）作为一种含有微量元素锌的硒酶，与阿尔茨海默症（AD）密切相关，但具体机制尚不清楚。我们前期的研究发现SelR与AD关键蛋白凝集素（Clu）存在相互作用，且两者相互作用可显著降低AD模型细胞胞内ROS水平，结合相关研究进展提出SelR可能通过Clu作用AD。本项目拟采用分子生物学、细胞生物学及生物信息学等手段，围绕SelR与Clu相互作用的构效关系在分子、细胞、动物水平展开研究，探索SelR通过Clu作用AD的机制。主要研究内容包括：1）SelR与Clu复合物的制备、结构解析及其对Ab的作用；2）SelR关键结构域与氨基酸对两者相互作用及AD相关指标的影响；3）在Clu基因沉默的AD模型细胞中表达SelR并研究其对AD的作用和Clu依赖性；4) SelR在AD模型鼠脑内表达及其对AD的作用和对Clu的影响。该项目将为SelR在预防及治疗AD中的有效利用提供坚实基础。

中文关键词： 相互作用；免疫共沉淀；复合物；调控机制

英文摘要： SelR, a unique zinc-containing selenoenzyme, is tightly associated with Alzheimer′ s disease (AD); however, the role and underlying mechanism of SelR in AD remain elusive. We have previously found that SelR directly interacted with the chaperone protein clusterin (Clu), which play a key role in AD, and this protein-protein interaction could significantly reduce intracellular ROS levels in an AD model cell line. In view of above results and recent progress in SelR and Clu, we propose the hypothesis that SelR may exert its effects via Clu. In this project, molecular biological, cell biological and bioinformatics techniques will be employed to study the structure-function on the interaction of SelR and Clu, aimed to explore the underlying mechanism how SelR intervenes AD via Clu at the molecular, cellular, and oragnismal levels. The studies includes 1) SelR-Clu protein complex preparation, structural analysis and function study; 2) roles of several critical motifs and residues in SelR on its interaction with Clu and AD pathological features; 3) effects and mechanisms of SelR on AD model cell and the dependence on Clu; 4) effects of SelR expression on the learning and cognitive abilities, as well as Clu expression of AD transgenic mouse. This project will provide important information for intensive study and efficient application of SelR.

英文关键词： interaction;co-immunoprecipitation;complex;regulation mechanism