DOI: 10.1002/ame2.12368
miRNA-137-5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin-specific peptidase 30
Yang Jiang1
Wei Bian2
Jing Chen3
Xiaopan Cao2
ChunYao Dong2
Ying Xiao2
Bing Xu3
XiaoHong Sun4
1.Department of Neurology,The First People 's Hospital of ShenYang,Shenyang,P.R. China;Department of Neurology,The Fourth Affiliated Hospital of China Medical University,Shenyang,P.R. China2.Department of Neurology,The First People 's Hospital of ShenYang,Shenyang,P.R. China3.Department of Neurology and Neuroscience,Shenyang Tenth People 's Hospital,Shenyang Chest Hospital,Shenyang,P.R. China4.Department of Neurology,The Fourth Affiliated Hospital of China Medical University,Shenyang,P.R. China;Science Experiment Center,China Medical University,Shenyang,China
摘要：Background : Alzheimer's disease (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 downstream 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- luciferase 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- induced 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.
机标关键词：alzheimerubiquitinspecificmemoryspatialmicecognitionimproves
论文发表日期：2023-12-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 526-536 )
英文信息