MiR-539-5p Decreases amyloid β-protein production, hyperphosphorylation of Tau and Memory Impairment by Regulating PI3K/Akt/GSK-3β Pathways in APP/PS1 Double Transgenic Mice.

Abstract

The production of amyloid β (Aβ) and tau hyperphosphorylation have been identified as key processes in Alzheimer's disease (AD) pathogenesis. MiR-539-5p has been found to be abnormally expressed in brain tissue; however, the functional role of miR-539-5p in the pathogenesis of AD remains unclear. In our study, we found that the expression of miR-539-5p was significantly downregulated in humans and mice with AD and was negatively correlated with expression of APP, caveolin 1, and GSK-3β. Moreover, upregulation of miR-539-5p inhibited Aβ accumulation, tau phosphorylation, oxidative stress, and apoptosis and improved memory ability in AD mice. Furthermore, by using bioinformatics tool and dual-luciferase reporter assay, APP, Caveolin 1, and GSK-3β were confirmed as direct targets of miR-539-5p. In addition, the PI3K/AKT/GSK-3β signaling pathway can be regulated by miR-539-5p. In conclusion, this study provided a novel insight into the pathologic mechanism of AD by identifying that miR-539-5p plays a neuroprotective role in AD.