突变和修饰β淀粉样蛋白与阿尔茨海默病  

Mutant and Modified AmyloidβPeptides and Alzheimer’s Disease

作　　者：郝秀萍 武林芝 HAO Xiu-Ping;WU Lin-Zhi(Department of Materials and Chemistry,Taiyuan University,Taiyuan 030032,China)

机构地区：[1]太原学院材料与化学工程系,太原030032

出　　处：《生物化学与生物物理进展》2022年第1期100-112,共13页Progress In Biochemistry and Biophysics

摘　　要：淀粉样蛋白级联假说是阿尔茨海默病(Alzheimer’s disease,AD)病因学的核心,但在过去几年中,靶向淀粉样斑块并未实现成功的免疫治疗。最近几年,不同形式的β淀粉样蛋白(Aβ)引起人们的关注。本文总结了关于早发性AD患者大脑中不同Aβ突变体和散发性AD患者大脑中已经鉴定出的经过酶切及修饰产生的不同形式Aβ的研究进展,重点阐述了这些Aβ的聚集特性和在AD发展中的影响,并对目前报道的Aβ变体检测分析方法进行了概述。本文旨在为今后深入研究不同形式的Aβ及相关分子在AD病理过程中的作用、开发诊断和治疗AD新方法提供参考。The amyloid cascade hypothesis is the core of etiology of Alzheimer’s disease(AD).However,in the past few years,immunotherapy targeting amyloid plaques has not been successful.In recent years,different forms of amyloidβpeptides(Aβ)have attracted people’s attention.Here,we summarized the research progress of different Aβmutants in the brains of early-onset AD patients and the truncated and modified Aβisoforms that have been identified in the brains of sporadic AD patients,particularly focusing on the aggregation characteristics of these Aβspecies and their impact on the process of AD.Single amino acid Aβmutations associated with FAD(familiar AD)lead to alterations in the structure of Aβ,which are associated with differential aggregation kinetics,morphologies,and conformations.These differences may underlie the pathological polymorphism of FAD.Meanwhile,enzyme digestion and post-transnational modification of Aβmay contribute to sporadic AD.Targeting these peptides or related enzymes can be used as a new therapeutic mechanism or provide a new diagnostic method.The currently reported detection and analysis methods of Aβspecies was also summarized,including traditional mass spectrometry,immunoassay methods,and electrochemistry methods.This review may contribute to the in-depth study of the role of different forms of Aβand related molecules in the pathological process of AD,and provide insight for the development of new methods for the diagnosis and treatment of AD.

关 键 词：阿尔茨海默病 突变Aβ 修饰Aβ 聚集特性 病理特性 检测方法 

分 类 号：Q4[生物学—生理学] R338[医药卫生—人体生理学]