Overexpression of miR-26a-5p Suppresses Tau Phosphorylation and Aβ Accumulation in the Alzheimer’s Disease Mice by Targeting DYRK1A

Author(s): Yanni Liu, Lin Wang, Fuheng Xie, Xiao Wang, Yuanyuan Hou, Xiaomeng Wang, Juan Liu*

Journal Name: Current Neurovascular Research

Volume 17 , Issue 3 , 2020


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Abstract:

Objective: It is reported that miR-26a-5p could regulate neuronal development, but its underlying mechanisms in Alzheimer’s disease (AD) progression is unclear.

Methods: APP (swe)/PS1 (ΔE9) transgenic mice served as AD mice. Morris water maze test was used to measure the spatial learning and memory ability of mice. The expressions of miR-26a-5p, DYRK1A, phosphorylated-Tau, Aβ40, and Aβ42 were detected. The relationship between miR- 26a-5p and DYRK1A was explored using dual luciferase reporter assay. The effects of miR-26a- 5p on AD mice was determined.

Results: AD mice walked a lot of wrong ways to find the platform area and the latency time to reach the platform was longer. There was low expression of MiR-26a-5p in AD mice. Overexpression of miR-26a-5p inhibited Tau phosphorylation and Aβ accumulation. MiR-26a-5p negatively regulated DYRK1A via targeting its 3’UTR. In vivo, increased miR-26a-5p down-regulated Aβ40, Aβ42, p-APP and p-Tau levels in AD mice through decreasing DYRK1A. Meanwhile, the swimming path and the latency time, to reach the platform, was shorten after enhancing miR-26a-5p expression.

Conclusion: Overexpression of miR-26a-5p could repress Tau phosphorylation and Aβ accumulation via down-regulating DYRK1A level in AD mice.

Keywords: Alzheimer's disease, miR-26a-5p, DYRK1A, Tau phosphorylation, Aβ accumulation, neurodegenerative disease.

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Article Details

VOLUME: 17
ISSUE: 3
Year: 2020
Published on: 28 September, 2020
Page: [241 - 248]
Pages: 8
DOI: 10.2174/1567202617666200414142637
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