Background: Accumulation of beta-amyloid (AB) 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 (TNF alpha)-induced protein 1 (TNFAIPI) at mRNA and protein levels in primary mouse cortical neurons and Neuro2a (N2a) cells exposed to different concentrations of A beta(25-35) 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-kappa B) activity and level, respectively. Results: A beta(25-35) downregulated miR-137 and upregulated TNFAIPI in primary mouse cortical neurons and N2a cells. In addition, miR-137 was found to directly target TNFAIPI and suppress its mRNA and protein levels. Moreover, miR-137 restoration and TNFAIPI knockdown facilitate A beta(25-35)-induced cell toxicity, apoptosis, caspase-3 activity, and activated NF-kappa B in N2a cells, which was partially abolished by TNFAIPI overexpression. Conclusion: miR-137 attenuated A beta-induced neurotoxicity through inactivation of NF-kappa B pathway by targeting TNFAIPI in N2a cells, shedding light on the molecular mechanism of miR-137 underlying A beta induced neurotoxicity. (C) 2017 Elsevier Inc. All rights reserved.