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

Background: Accumulation 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.

Methods: Serum 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.

Results: miR-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.

Conclusion: miR-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.