miR-137 attenuates Aβ-induced neurotoxicity through inactivation of NF-κB pathway by targeting TNFAIP1 in Neuro2a cells.

BACKGROUND: Accumulation of β-amyloid (Aβ) and neuroinflammation are implicated in the pathogenesis and development of Alzheimer's disease (AD). Neuron-enriched miR-137 was aberrantly downregulated and may be associated with the pathogenesis of AD. However, the detailed function of miR-137 in AD pathogenesis and the molecular mechanism have not been elucidated.

METHODS: The expressions of miR-137 and tumor necrosis factor alpha (TNFα)-induced protein 1 (TNFAIP1) at mRNA and protein levels in primary mouse cortical neurons and Neuro2a (N2a) cells exposed to different concentrations of Aβ25-35 were examined by qRT-PCR and western blot. Luciferase reporter assay was used to confirm the potential target of miR-137. MTT assay, flow cytometry analysis, caspase-3 activity assay, Enzyme-linked immunosorbent assay (ELISA), and western blot were used to detect cell viability, apoptosis, caspase-3 activity, Nuclear factor-kappa B (NF-κB) activity and level, respectively.

RESULTS: Aβ25-35 downregulated miR-137 and upregulated TNFAIP1 in primary mouse cortical neurons and N2a cells. In addition, miR-137 was found to directly target TNFAIP1 and suppress its mRNA and protein levels. Moreover, miR-137 restoration and TNFAIP1 knockdown facilitate Aβ25-35 -induced cell toxicity, apoptosis, caspase-3 activity, and activated NF-κB in N2a cells, which was partially abolished by TNFAIP1 overexpression.

CONCLUSION: miR-137 attenuated Aβ-induced neurotoxicity through inactivation of NF-κB pathway by targeting TNFAIP1 in N2a cells, shedding light on the molecular mechanism of miR-137 underlying Aβ-induced neurotoxicity.