MiR-34a-5p and miR-125b-5p attenuate Aβ-induced neurotoxicity through targeting BACE1

Abstract

BackgroundAccumulation of β-amyloid (Aβ) could induce neurotoxicity in Alzheimer's disease (AD). microRNA (miR)-34a-5p and miR-125b-5p have been reported to be aberrantly expressed in AD patients. However, the roles and mechanisms of these two miRNAs in AD remain poorly understood. MethodsSerum samples of 27 AD patients were collected. Primary mouse cortical neurons (MCN) and Neuro2a (N2a) cells were incubated with Aβ. The expression levels of miR-34a-5p, miR-125b-5p and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) were detected by quantitative real-time polymerase chain reaction and western blot. The effect of miRNAs or epigallocatechin-3-gallate (EGCG) on Aβ-induced neurotoxicity was investigated by cell viability, Caspase 3 activity, apoptosis and intracellular ROS production. The interaction between BACE1 and miR-34a-5p or miR-125b-5p was analyzed by luciferase reporter assay. ResultsmiR-34a-5p and miR-125b-5p levels were decreased and BACE1 mRNA expression was increased in AD patients and Aβ-treated MCN and N2a cells. Addition of miR-34a-5p or miR-125b-5p attenuated Aβ-induced apoptosis and oxidative stress. BACE1 acted as a target of miR-34a-5p and miR-125b-5p and its restoration weakened the effect of miR-34a-5p or miR-125b-5p on Aβ-induced neurotoxicity. Moreover, EGCG could mitigate Aβ-induced neurotoxicity, which might be associated with miR-34a-5p and miR-125b-5p. ConclusionmiR-34a-5p and miR-125b-5p inhibited Aβ-induced neurotoxicity by decreasing apoptosis and oxidative stress via targeting BACE1, providing novel targets for treatment of AD.