Beta Amyloid Peptide: Research Paper : MicroRNA-140 silencing represses the incidence of Alzheimer's disease

MicroRNA-140 silencing represses the incidence of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition leading to severe disability from progressive impairments in cognitive functions including memory and learning. Non-coding microRNAs (miRNAs or miRs) have been linked to the pathogenesis of AD. The present study aimed to investigate the clinical significance and biological function of miR-140 in AD. First, we examined the expression of miR-140 and PINK1 in brain tissues of the established AD model rats and neurons cultured with Aβ-derived diffusible ligands (AβDDLs). We identified an interaction between miR-140 and PINK1, and measured spatial learning and memory abilities of the model rats using the Morris water maze (MWM) test. After ectopic expression and depletion experiments in neurons and AD rats, we measured the levels of reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), along with mTOR expression and phosphorylation, and autophagy-related factors. Results showed up-regulation of miR-140 and down-regulation of PINK1 in AD model rats and neurons. PINK1 was verified to be a direct target of miR-140, and silencing of miR-140 suppressed mitochondrial dysfunction, and enhanced autophagy in AD model rats and neurons, as supported by decreased levels of mTOR expression and phosphorylation, β-amyloid p-Tau (Ser396), p-Tau (Thr231), Tau and ROS, and increased MMP levels and expression of Beclin 1 expression and LC3-II/LC3-I. Collectively, functional suppression of miR-140 enhanced autophagy and prevented mitochondrial dysfunction by upregulating PINK1, ultimately suggesting a novel therapeutic target for AD.

Keywords: Alzheimer's disease; Autophagy; MicroRNA-140; Mitochondrial dysfunction; PINK1.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33529652/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.