Aβ寡聚体与阿尔茨海默病  

Aβoligomer and Alzheimer's disease

作　　者：刘志安 林燕玲 韩爱东[1] LIU Zhian;LIN Yanling;HAN Aidong(School of Life Sciences,Xiamen University,Xiamen 361100,China)

机构地区：[1]厦门大学生命科学学院,福建厦门361100

出　　处：《中山大学学报（自然科学版）（中英文）》2022年第3期1-10,共10页Acta Scientiarum Naturalium Universitatis Sunyatseni

摘　　要：阿尔茨海默病(AD,Alzheimer's disease)是老年人常见的神经退行性疾病(neurodegenerative diseases),也是痴呆症(dementia)最常见的病因。其主要症状是记忆衰退(memory loss)和进行性认知障碍(progressive cogni‐tive impairment)。β-淀粉样蛋白(Aβ,amyloid β)是一种AD发病的关键蛋白。Aβ在各类脑组织中的超常积累以及聚集形成的β-淀粉样斑块导致AD的发生发展,是过去具有巨大影响力的“淀粉样级联假说”(amyloid cascade hypothesis)的核心观点。但最新的证据表明,Aβ寡聚体(AβO,Aβ oligomer)才是真正诱发AD的神经毒素。本文综述了β-淀粉样蛋白研究的最新进展,重点介绍了Aβ的产生和聚集过程和Aβ寡聚体的分类及其神经毒性。最后,本文还介绍了近些年来基于毒性Aβ寡聚体开发治疗AD药物的研究进展。Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and also the most common cause of dementia.The main symptoms are memory loss and progressive cognitive impairment.Amyloidβ(Aβ)is one of the key proteins in the AD pathogenesis.The occur‐rence and development of AD caused by the accumulation of Aβand the abnormal accumulation ofβ-amyloid plaques in various brain tissues was once regarded as the"amyloid cascade hypothesis"for AD pathogenesis.However,more recent evidences suggest that Aβoligomers are in fact neurotoxins,leading to an"Aβoligomer hypothesis",where toxic Aβoligomers trigger brain damages that causes the AD pathogenesis.Here we review the latest research progresses onβ-amyloid protein,focusing on the process of production and aggregation of Aβ,and the classification and neurotoxicity of the Aβoligomers.We further highlight new AD therapeutic strategies targeting the toxic Aβoligomers,as exemplified by anti-Aβmonoclonal antibodies approved for clinic usage in recent years.

关 键 词：阿尔茨海默病 APP AΒ寡聚体 神经毒性 aducanumab 

分 类 号：R749.16[医药卫生—神经病学与精神病学]