MicroRNA-322 Cluster Promotes Tau Phosphorylation via Targeting Brain-Derived Neurotrophic Factor.

MicroRNA-322 Cluster Promotes Tau Phosphorylation via Targeting Brain-Derived Neurotrophic Factor. Neurochem Res. 2018 Feb 20;: Authors: Zhang J, Liu Z, Pei Y, Yang W, Xie C, Long S Abstract Brain-derived neurotrophic factor (BDNF) is a crucial regulator to support synaptic plasticity and neuronal survival, its significant decrease is a pathophysiological hallmark in Alzheimer's disease (AD) brains and accounts for poor prognosis. MicroRNAs (miRNAs) interfere with the translation of target mRNAs and control a variety of physiological and pathological processes. MiR-322 is the rodent homologue of human miR-424, it is involved in the modulation of cell differentiation, proliferation, apoptosis and metabolic activities in diverse tissues and organs. However, the roles and potential mechanisms of miR-322 remain elusive in AD pathogenesis. Here we observed miR-322 is significantly increased along with BDNF decrease in AD mouse brain. Bioinformatics prediction implicated that BDNF 3'-untranslated region (3'-UTR) possesses the putative target sequence of miR-322. Luciferase reporter assay identified that miR-322 can directly conjugate to BDNF 3'-UTR. The functional research showed that MiR-322 input deregulates BDNF expression at either mRNA or protein levels, whereas miR-322 silence restores BDNF expression in vitro. Furthermore, we found miR-322 promotes Tau phosphorylation via negatively controlling BDNF-TrkB receptor activation, otherwi...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research