miR-26a-5p 的过表达通过靶向 DYRK1A 抑制阿尔茨海默病小鼠 Tau 磷酸化和 Aβ 积累。

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

机构信息

Department of Neurology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712000, China.

Department of Neurology, The First Affiliated Hospital of Xi'an Medical University, Xi'an City, Shaanxi Province, 710077, China.

出版信息

Curr Neurovasc Res. 2020;17(3):241-248. doi: 10.2174/1567202617666200414142637.

DOI:10.2174/1567202617666200414142637

PMID:32286945

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.

摘要

目的

有报道称 miR-26a-5p 可调节神经元发育，但它在阿尔茨海默病（AD）进展中的潜在机制尚不清楚。

方法

APP（swe）/PS1（ΔE9）转基因小鼠作为 AD 小鼠。采用 Morris 水迷宫试验检测小鼠的空间学习和记忆能力。检测 miR-26a-5p、DYRK1A、磷酸化 Tau、Aβ40 和 Aβ42 的表达。采用双荧光素酶报告基因检测 miR-26a-5p 与 DYRK1A 之间的关系。探讨 miR-26a-5p 对 AD 小鼠的影响。

结果

AD 小鼠在寻找平台区域时走了很多错误的路，到达平台的潜伏期时间较长。AD 小鼠中 MiR-26a-5p 表达水平较低。过表达 miR-26a-5p 可抑制 Tau 磷酸化和 Aβ 积累。MiR-26a-5p 通过靶向 DYRK1A 的 3'UTR 负调控 DYRK1A。体内，通过降低 DYRK1A，增加的 miR-26a-5p 可降低 AD 小鼠中 Aβ40、Aβ42、p-APP 和 p-Tau 的水平，从而降低 Aβ40、Aβ42、p-APP 和 p-Tau 的水平。同时，增强 miR-26a-5p 表达后，小鼠的游泳路径和到达平台的潜伏期时间缩短。