miRNAs靶向调控Aβ生成的机制研究进展  

Targeted regulation of Aβgeneration by miRNAs:the current advances

作　　者：杞燕梅 苏建培 汪旭[1] 郭锡汉[1] QI Yan-Mei;SU Jian-Pei;WANG Xu;GUO Xi-Han(School of Life Science,Engineering Research Center of Sustainable Development and Utilization of Biomass Energy,Ministry of Education,Yunnan Normal University,Kunming 650500,China;Department of Geriatrics,Kunming Second People's Hospital,Kunming 650500,China)

机构地区：[1]云南师范大学生命科学学院,生物能源持续开发与利用教育部工程研究中心,昆明650500 [2]昆明市第二人民医院老年一科,昆明650500

出　　处：《生命科学》2022年第9期1116-1125,共10页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(31860301,31900410);云南省基础研究计划(202001AU070055);云南师范大学优秀青年学者项目。

摘　　要：miRNAs是一类内源性的、长度为19~24 nt的非编码RNA,可特异性地靶向基因并在转录后调控基因的表达,在发育和组织内稳态中发挥重要的调节作用。近期,越来越多的证据表明部分miRNAs的异常表达在衰老和阿尔茨海默病(Alzheimer’s disease,AD)等神经退行性疾病中起关键作用。作为AD患者最显著的病理特征和AD发生发展的主导因素之一,β淀粉样蛋白(β-amyloid protein,Aβ)的大量产生与miRNAs的表达异常息息相关。Aβ由淀粉样前体蛋白(APP)经β-分泌酶(BACE1)和γ-分泌酶(其催化亚基为PSEN1)剪切而成。此外,α-分泌酶(ADAM10)可与β-分泌酶竞争性剪切APP,从而抑制Aβ的产生。本文就靶向调控APP、BACE1、PSEN1和ADAM10基因表达的miRNAs及其作用机制的研究进展进行综述,为今后探索AD的临床诊断手段和潜在的治疗靶点提供理论依据。The microRNAs(miRNAs),a class of endogenous non-coding RNAs with a length of 19-24 nt,can specifically bind to the mRNA of target genes and regulate the expression of target genes at the post-transcriptional level.Through fine tuning gene expression,miRNAs play critical roles in physiological development and tissue homeostasis.miRNAs expression significantly alters during cellular aging and neurodegeneration.Recently,increasing evidence has revealed some of the de-expressed miRNAs exert essential roles in aging and neurodegenerative diseases such as Alzheimer’s disease(AD).As the most significant pathological feature of AD brain and a risk factor for AD initiation and development,increased production ofβ-amyloid protein(Aβ)is tightly associated with miRNA de-expression.Aβis produced from a stepwise cleavage of the amyloid precursor protein(APP),which is mediated byβ-secretase(BACE1)andγ-secretase(its catalytic subunit PSEN1).In addition,α-secretase(ADAM10)can compete with BACE1 to cleave APP,thereby reducing Aβproduction in this pathway.Herein,we summarize the miRNAs that can specifically target and regulate the expression of APP,BACE1,PSEN1and ADAM10,and discuss the underlying molecular mechanisms.Understanding this biological process may provide a framework to explore the potential clinical diagnostic methods and therapeutic targets for AD.

关 键 词：MIRNAS 淀粉样前体蛋白 Β-分泌酶 Γ-分泌酶 Α-分泌酶 

分 类 号：R741[医药卫生—神经病学与精神病学]