阿尔茨海默病中β淀粉样蛋白的生成及清除的调节  

Regulation of Amyloidogenesis and Clearance of β-Amyloid in Alzheimer’s Disease

作　　者：崔雨婷 王亚琦 王培昌[1] CUI Yu-Ting;WANG Ya-Qi;WANG Pei-Chang(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》2021年第2期176-181,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.81871714,81901406);北京市博士后工作经费资助项目(No.ZZ2019-13)资助。

摘　　要：阿尔茨海默病(Alzheimer’s disease, AD)是一种慢性退行性神经系统疾病,临床主要表现为进行性认知能力下降、记忆力衰退、人格改变等。AD的标志性病理特征包括脑细胞外β淀粉样蛋白(β-amyloid protein, Aβ)沉积形成老年斑、细胞内神经纤维缠结(neurofibrillary tangles, NFT)、神经炎症增加以及神经元凋亡。β淀粉样蛋白主要在神经元产生,是淀粉样前体蛋白经过一系列酶解反应生成的由39~42个氨基酸组成的多肽,调节Aβ的生成和清除能够有效延缓甚至逆转阿尔茨海默病的进程,因而具有重大的研究价值。β-分泌酶(β-site APP cleaving enzyme 1,BACE1)为Aβ产生过程中的关键酶,其含量及活性的改变均能影响Aβ产生,在阿尔茨海默病的发生发展中发挥至关重要的作用;老年斑周围炎性细胞的聚集提示,AD与神经炎症高度相关,神经炎症相关细胞能够参与Aβ的清除,多种炎性因子也能调节Aβ的生成;非编码RNA虽很少直接参与Aβ的产生、沉积和清除,但其可以通过多种途径调节Aβ的产生。本文从β淀粉样蛋白生成及清除的机制着手,重点阐述了BACE1、神经炎症、非编码RNA对Aβ调控的重要作用,以期为AD发病机制的进一步研究提供思路,并对阿尔茨海默病早期干预及治疗提供理论参考。Alzheimer’s disease(AD), an age-associated chronic progressive neurodegeneration disorder, is characterized by progressive loss of memory, cognitive impairment and behavioral changes. The pathological hallmarks of AD are β-amyloid(Aβ) deposition, neurofibrillary tangles induced by phosphorylation of tau protein, upregulation of inflammation and neuronal apoptosis. β-Amyloid is a polypeptide consisting of 39-42 amino acids which is produced by a series of enzymatic hydrolysis of amyloid precursor protein in neurons. Studying the regulation of the production and clearance of Aβ is of great importance which may help in finding potential intervention to effectively delay or even reverse the process of Alzheimer’s disease. As the key enzyme of Aβ production, β-secretase(β-site APP cleaving enzyme 1, BACE1) plays an essential role in the development of AD. The aggregation of inflammatory cells around senile plaques suggests that Aβ is highly associated with neuroinflammation. Neuroinflammation-related cells participate in the clearance of Aβ and multiple cytokines regulate the level of Aβ. In addition, although non-coding RNA is rarely involved in the production, deposition and clearance of Aβ directly, it can regulate the production of Aβ through other pathways. In this article, we will focus on the important role of BACE1, neuroinflammation and non-coding RNA in the regulation of Aβ and review the mechanism of production and clearance of Aβ in AD.

关 键 词：阿尔茨海默病 Β淀粉样蛋白 神经炎症 非编码RNA Β-分泌酶 

分 类 号：R34[医药卫生—基础医学]