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

[ Vol. 17 , Issue. 3 ]

Author(s):

Yanni Liu, Lin Wang, Fuheng Xie, Xiao Wang, Yuanyuan Hou, Xiaomeng Wang and Juan Liu*   Pages 241 - 248 ( 8 )

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.

Affiliation:

Department of Neurology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712000, Department of Neurology, The First Affiliated Hospital of Xi’an Medical University, Xi’an City, Shaanxi Province, 710077, Department of Neurology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712000, Department of Neurology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712000, Department of Neurology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712000, Department of Neurology, The First Affiliated Hospital of Xi’an Medical University, Xi’an City, Shaanxi Province, 710077, Department of Neurology, The First Affiliated Hospital of Xi’an Medical University, Xi’an City, Shaanxi Province, 710077



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