miRNA-137-5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin-specific peptidase 30  

作　　者：Yang Jiang Wei Bian Jing Chen Xiaopan Cao ChunYao Dong Ying Xiao Bing Xu XiaoHong Sun 

机构地区：[1]Department of Neurology,The First People's Hospital of ShenYang,Shenyang,P.R.China [2]Department of Neurology,The Fourth Affiliated Hospital of China Medical University,Shenyang,P.R.China [3]Department of Neurology and Neuroscience,Shenyang Tenth People's Hospital,Shenyang Chest Hospital,Shenyang,P.R.China [4]Science Experiment Center,China Medical University,Shenyang,China

出　　处：《Animal Models and Experimental Medicine》2023年第6期526-536,共11页动物模型与实验医学（英文）

基　　金：Liaoning Province Science and Technology Project(grant/award number:2019-BS-221);Shenyang Science and Technology Project(grant/award number:19-112-4-040)。

摘　　要：Background:Alzheimer’sdisease(AD)is a prevalent neurodegenerative disorder causing progressive dementia.Research suggests that microRNAs(miRNAs)could serve as biomarkers and therapeutic targets for AD.Reduced levels of miR-137 have been observed in the brains of AD patients,but its specific role and down stream mechanisms remain unclear.This study sought to examine the therapeutic potential of miR-137-5p agomir in alleviating cognitive dysfunction induced in AD models and explore its potential mechanisms.Methods:This study utilized bioinformatic analysis and a dual-l uciferase reporter assay to investigate the relationship between miR-137-5p and ubiquitin-specific peptidase 30(USP30).In vitro experiments were conducted using SH-SY5Y cells to assess the impact of miR-137-5p on Aβ1-42 neurotoxicity.In vivo experiments on AD mice evaluated the effects of miR-137-5p on cognition,Aβ1-42 deposition,Tau hyperphosphorylation,and neuronal apoptosis,as well as its influence on USP30 levels.Results:It was discovered that miR-137-5p mimics efficiently counteract Aβ1-42 neurotoxicity in SH-SY5Y cells,a protective effect that is negated by USP30 overexpression.In vivo experiments demonstrated that miR-137-5p enhances the cognition and mobility of AD mice,significantly reducing Aβ1-42 deposition,Tau hyperphosphorylation,and neuronal apoptosis within the hippocampus and cortex regions.Mechanistically,miR-137-5p significantly suppresses USP30 levels in mice,though USP30 overexpression partially buffers against miR-137-5p-i nduced AD symptom improvement.Conclusion:Our study proposes that miR-137-5p,by instigating the downregulation of USP30,has the potential to act as a novel and promising therapeutic target for AD.

关 键 词：Alzheimer's disease AΒ1-42 miR-137-5p USP30 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]