MiR-137 overexpression protects neurons from Aβ-induced neurotoxicity via ERK1/2

Abstract

Accumulation of amyloid-β (Aβ) is implicated in the pathogenesis and development of Alzheimer's disease (AD) and it is a prime suspect for causing neuronal loss and cognitive deficits during AD. To explore the mechanisms of Aβ-induced neurodegeneration, we used Aβ-treated primary cortical neuron culture as a cell model of AD and investigated the function of miR-137 in this process. qRT-PCR and western blot were used to examine levels of miR-137, AMPA receptors (AMPARs), p-ERK1/2, and ERK1/2. MTT assay and caspases 3 activity assay were employed to examine cell viability and apoptosis. Dual-luciferase assay was used to validate the interaction between miR-137 and ERK1/2. We found that Aβ decreased cell viability, AMPAR and miR-137 levels, but increased caspase 3 activity in a dose- and time-dependent manner. Overexpression of miR-137 suppressed the Aβ-induced neurotoxicity. MiR-137 directly bound to ERK1/2 mRNA and negatively regulated its expression. Further, overexpression of ERK1/2 blocked the effects of miR-137 mimics on Aβ-induced neurotoxicity. These results provide strong evidence that miR-137 protects neurons against Aβ-induced neurotoxicity via targeting ERK1/2.