多肽介导的泛素-蛋白酶体系统特异性降解Tau蛋白  

Specific Knockdown of Endogenous Tau Protein by Peptide Directed Ubiquitin Proteasome Degradation

作　　者：Ting-Ting Chu Na Gao Qian-Qian Li Pu-Guang Chen Xi-Fei Yang 陈永湘[2] Yu-Fen Zhao 李艳梅[2] 

机构地区：[1]不详 [2]清华大学化学系

出　　处：《科学新闻》2017年第4期169-169,共1页Science News

基　　金：科技部国家重大科学研究计划;国家自然科学基金;教育部科学基金;北京脑重大疾病研究院的资助

摘　　要：Tau蛋白是阿尔兹海默症（Alzheimer’s disease，AD）重要的病理相关蛋白，可介导AB的毒性。该蛋白是一种无固定结构的非酶蛋白，通常被称为“undruggable”蛋白，难以设计调控该蛋白质的含量和活性的靶向分子。Tau, an important pathological protein of Alzheimer's disease (AD), can mediate the toxicity of amyloid beta (A beta). Thus, reduction of Tau with chemical molecules may offer a novel strategy for treating AD. Here, we designed and synthesized a series of multifunctional molecules that contained Tau-recognition moieties and E3 ligase-binding moieties to enhance Tau degradation. Among these molecules, TH006 had the highest activity of inducing Tau degradation by increasing its poly-ubiquitination. The decrement in Tau induced by TH006 could decrease the cytotoxicity caused by Ab. Furthermore, TH006 could regulate the Tau level in the brain of an AD mouse model. Therefore, partial reduction of Tau with such multifunctional peptides may open up a novel therapeutic strategy for AD treatment.

关 键 词：蛋白酶 降解 异性 系统 固定结构 蛋白质 

分 类 号：TQ925.2[轻工技术与工程—发酵工程]