Inhibition of miR-25-3p Alleviates Neuroinflammation in Alzheimer's Disease By Targeting ADAM10

As a neurodegenerative disorder, Alzheimer's disease (AD) is defined by progressive cognitive decline and involves intricate pathological mechanisms. This study aimed to investigate the clinical role and regulatory mechanism of miR-25-3p in AD. This investigation enrolled 115 AD patients and 110 healthy control subjects. Serum levels of miR-25-3p were quantified using quantitative real-time PCR (qRT-PCR), and the diagnostic performance of miR-25-3p for AD was assessed via receiver operating characteristic (ROC) analysis. In vitro, cellular models of AD were established by treating SH-SY5Y and HMC3 cells with amyloid-beta peptide 25-35 (Aβ25-35). Cellular proliferation and apoptosis were evaluated using the CCK-8 assay and flow cytometry, respectively. ELISA was employed to measure the concentrations of pro-inflammatory and anti-inflammatory cytokines. Furthermore, the direct targeting relationship between miR-25-3p and ADAM10 was confirmed through dual-luciferase reporter assays. miR-25-3p was significantly upregulated in the serum of AD patients and Aβ25-35-induced AD cell models, suggesting its potential diagnostic relevance for AD. Inhibition of miR-25-3p attenuated Aβ25-35-mediated neurotoxicity and neuroinflammation, whereas ADAM10 knockdown abrogated the neuroprotective effects of the miR-25-3p inhibitor in SH-SY5Y and HMC3 cells, which suggests that inhibition of miR-25-3p may alleviate the disease progression of AD by targeting ADAM10. Therefore, inhibition of miR-25-3p may alleviate the disease progression of AD by targeting ADAM10, providing a novel potential regulatory axis for AD intervention.