磷酸化Tau蛋白的聚集动力学与影响因素研究  

Aggregation kinetics and influencing factors of phosphorylated Tau proteins

作　　者：陈燕歌 滕宁宁 武影影 李森 CHEN YanGe;TENG NingNing;WU YingYing;LI Sen(Gene engineering and Biotechnology Beijing Key Laboratory,National Demonstration Center for Experimental Life Sciences&Biotechnology Education,College of Life Sciences,Beijing Normal University,Beijing 100875,China)

机构地区：[1]北京师范大学生命科学学院,基因工程药物及生物技术北京市重点实验室,生命科学与技术国家级实验教学示范中心,北京100875

出　　处：《中国科学：生命科学》2022年第8期1261-1268,共8页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:31570756,32071222);北京市教育委员会共建项目资助。

摘　　要：阿尔茨海默症是对老年人威胁巨大的一种神经退行性疾病,已有研究表明Tau蛋白的异常磷酸化和聚集与该疾病密切相关.本文利用硫黄素T(Thioflavin T,ThT)荧光光谱技术,探究了发生异常磷酸化修饰的pTau蛋白的体外聚集过程,对所得数据进行了系统的动力学分析,并在此基础上研究了已形成的pTau寡聚体种子、温度、金属离子、大分子拥挤试剂等因素对pTau蛋白聚集动力学的影响作用,发现pTau蛋白的聚集过程由成核阶段与延伸阶段组成,其动力学曲线为S形,寡聚体种子的存在、温度的升高、Al^(3+)与大分子拥挤试剂的加入可以显著促进pTau蛋白的聚集,且其对pTau蛋白成核阶段的影响作用大于对其延伸阶段的影响作用.Alzheimer’s disease(AD)is a common cause of dementia among elders.Hyperphosphorylation and aggregation of Tau correlate with the clinical progression of AD.In this study,the Thioflavin T fluorescence spectroscopy was used to explore the aggregation kinetics of pTau protein in vitro.The effects of pTau oligomer seeds,temperature,metal ions,and macromolecular crowding agents on the aggregation kinetics were also studied.The results indicated that the aggregation of pTau protein accords with the sigmoidal equation of the nucleation-elongation model.The presence of oligomer seeds,increase in temperature,addition of Al^(3+),and macromolecular crowding reagents considerably promote the aggregation of pTau protein.Moreover,the effect on the rate of pTau nucleation was stronger than that of elongation.

关 键 词：阿尔茨海默症 TAU蛋白 聚集动力学 种子 大分子拥挤 

分 类 号：R749.16[医药卫生—神经病学与精神病学]