阿尔茨海默病中蛋白质相互作用对β-分泌酶的调节机制  

Regulatory Mechanism ofβ-Secretase by Protein Interactions in Alzheimer’s Disease

作　　者：刘聪聪 王培昌[1] 王亚琦 LIU Cong-Cong;WANG Pei-Chang;WANG Ya-Qi(Clinical Laboratory of Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院检验科,北京100053

出　　处：《中国生物化学与分子生物学报》2023年第1期54-61,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金重点项目(No.82030064);国家自然科学基金(No.82102487)资助。

摘　　要：阿尔茨海默病(Alzheimer’s disease,AD)是一种慢性神经退行性疾病,目前尚无有效的治疗方案。AD发病机制十分复杂,学说众多,目前较为公认的仍然是淀粉样蛋白级联假说。该学说认为,淀粉样斑块在脑组织的沉积是AD发病的关键病理机制。β-分泌酶(β-site APP cleaving enzyme 1,BACE1)是淀粉样前体蛋白(amyloid precursor protein,APP)淀粉样降解途径中的限速酶,其降解产物β-淀粉样蛋白(β-amyloid protein,Aβ)是淀粉样斑块(amyloid plaques)的主要成分。AD患者大脑BACE1浓度和活性增加,是引起AD的重要因素。因此,探究BACE1生成及活性调节的影响因素不仅对于理解AD的发病机制至关重要,而且对于开发AD的新治疗靶点也有重要意义。蛋白质之间的相互作用在蛋白质参与的各种生物学过程中发挥着重要的作用,因而被广泛研究。BACE1的相互作用蛋白质可以通过直接结合、间接结合和参与各种细胞信号转导通路等方式直接或间接地在BACE1的转录、翻译、修饰与胞内运输等各个环节对BACE1进行调节,从而影响AD的发生与疾病的进程。本文将从BACE1的生物学功能,以及相互作用蛋白质对BACE1的转录、翻译、细胞内转运及其活性与降解的调节作用进行综述,探讨BACE1生理功能与活性的影响因素,以及BACE1互作蛋白质调控BACE1的作用机制,旨在为理解AD的发病机制以及药物研发提供新的思考。Alzheimer’s disease(AD)is a chronic neurodegenerative disease while there is currently no effective treatment.The pathogenesis of AD is complex and there are numerous theories,of which,the deposition of amyloid plaques in brain tissue is still considered as the key pathological mechanism of AD.β-site APP cleaving enzyme 1(BACE1)is the rate-limiting enzyme in the amyloidogenic pathway of amyloid precursor protein(APP),and its degradation productβ-amyloid protein(Aβ)is the main component of amyloid plaque.Increased BACE1 concentration and activity in the brain of AD patients are important factors in causing AD.Thus,investigating the influencing factors of BACE1 is especially crucial not only for understanding the pathogenesis of AD,but also for developing new targets for AD.Interactions between proteins play an important role in various biological processes and are thus extensively studied.The interacting proteins of BACE1 regulate BACE1 activity via the processes of transcription,translation,modification,and intracellular transport of BACE1 through direct or indirect binding,and participating in various cell signal transduction pathways,thus affecting the occurrence and the process of AD.In this paper,the biological function of BACE1 and the regulatory effects of interacting proteins on the transcription,translation,intracellular transport,activity and degradation of BACE1 were reviewed.The influencing factors of the physiological function and activity of BACE1 and the mechanism of interaction protein regulating BACE1 were also summarized.This study aims to provide new thought for the mechanism of AD pathogenesis and drug development.

关 键 词：阿尔茨海默病 Β-分泌酶 相互作用蛋白质 调节机制 

分 类 号：R34[医药卫生—基础医学]