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

Neurochemical Research
Jun ZhangShiqi Long

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 ...Continue Reading

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Citations

Sep 26, 2020·Frontiers in Molecular Neuroscience·Wei WeiHao Li
Mar 19, 2020·Metabolic Brain Disease·Shamseddin AhmadiSteven Bradburn
May 17, 2019·Neural Plasticity·Chao-Chao YuLi-Hong Kong
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Aug 2, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Paula MoyanoJavier Del Pino

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Methods Mentioned

BETA
transgenic
PCR
GTPase
transfection
Assay

Software Mentioned

miRnada
GraphPad Prism
Pictar
Target scan

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