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.
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.
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.