Abstract
Background: microRNA-4284 is associated with various diseases, but its role in Alzheimer's disease remains unclear. This study explores the therapeutic potential of miR-4284 inhibition by targeting the APBA1 and the JAK/STAT3 pathways in AD models. Results: miR-4284 expression was analyzed in Aβ-treated SH-SY5Y cells and 5xFAD mice. Luciferase assays identified APBA1 as a direct target of miR-4284. Apoptosis, inflammation, and neuronal survival were assessed using qPCR, western blotting analysis, FACS, and immunohistochemistry. The Morris water maze test evaluated cognitive function, while western blotting analysis examined the JAK/STAT3 pathway. miR-4284 was upregulated in AD models. Its inhibition increased APBA1 expression, reduced Aβ accumulation, suppressed apoptosis and inflammation, and enhanced neuronal survival and cognitive function, correlating with JAK/STAT3 activation. Conclusions: miR-4284 inhibition confers neuroprotection by modulating APBA1 and JAK/STAT3 signaling, suggesting its potential as a therapeutic target for AD.