MicroRNA-326 decreases tau phosphorylation and neuron apoptosis through inhibition of the JNK signaling pathway by targeting VAV1 in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive and age-related neurological dysfunction. Abundant data have profiled microRNA (miR) patterns in healthy, aging brain, and in the moderate and late-stages of AD. Herein, this study aimed to explore whether miR-326 could influence neuron apoptosis in AD mice and how miR-326 functions in this process. The candidate differentially expressed gene VAV1 was obtained by microarray analysis, and miRNAs that could regulate VAV1 candidate gene were predicted. Luciferase activity determination confirmed VAV1 as a target gene of miR-326. AD mice models were established for investigating the effect of miR-326 on AD mice. The overexpression of miR-326 contributed to decreased time of the mice to find the platform and the escape latency and increased residence time on the target area. Besides, elevation of miR-326 decreased Aβ deposition and contents of Aβ1-40 and Aβ1-42 . Moreover, miR-326 overexpression increased neuron cell ability, mediated cell entry, and inhibited neuron apoptosis via JNK signaling pathway. Of crucial importance, miR-326 negatively regulated the expression of VAV1, inhibited tau phosphorylation, and blocked the activation of the JNK signaling pathway. Taken together these observations, we demonstrate that miR-326 improves cognitive function of AD mice and inhibits neuron apoptosis in AD mice through inactivation of the JNK signaling pathway by targeting VAV1. Based on those findings, miR-326 might exert promise as target for the treatment of AD.