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

• Published in: Current neurovascular research Vol. 17; no. 3; p. 241
• Main Authors: Liu, Yanni, Wang, Lin, Xie, Fuheng, Wang, Xiao, Hou, Yuanyuan, Wang, Xiaomeng, Liu, Juan
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2020
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Animals; Cell Line, Tumor; Dyrk Kinases; Gene Expression; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; MicroRNAs - biosynthesis; MicroRNAs - genetics; Phosphorylation - physiology; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - biosynthesis; Protein Serine-Threonine Kinases - genetics; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - biosynthesis; Protein-Tyrosine Kinases - genetics; tau Proteins - antagonists & inhibitors; tau Proteins - genetics; tau Proteins - metabolism; Tau phosphorylation; DYRK1A; neurodegenerative disease; miR-26a-5p; Alzheimer's disease; Aβ accumulation
• ISSN: 1875-5739
• DOI: 10.2174/1567202617666200414142637

It is reported that miR-26a-5p could regulate neuronal development, but its underlying mechanisms in Alzheimer's disease (AD) progression is unclear. 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. 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. Overexpression of miR-26a-5p could repress Tau phosphorylation and Aβ accumulation via down-regulating DYRK1A level in AD mice.