Amyloid-β25-35 Upregulates Endogenous Neuroprotectant Neuroglobin via NFκB Activation in vitro.

Neuroglobin (Ngb) has been reported to be increased in early and moderately advanced Alzheimer's disease (AD) stages but declined in the severe stage. However, its regulatory mechanisms and pathophysiological roles in the disease remain to be defined. In this study, we found that Ngb expression was significantly upregulated by low dose Aβ25-35, the neurotoxic fragment of Aβ1 - 40 and Aβ1 - 42, but was not further increased by a higher dose of Aβ25-35. Mutation analysis and supershift assay demonstrated that transcription factor Nuclear Factor κB (NFκB), κB2 and κB3 sites located in mouse Ngb promoter region were involved in dynamic regulation of Ngb expression in response to different doses of Aβ25-35 stimulation. In addition, we found that suppression of endogenous Ngb expression exacerbated Aβ25-35-induced neuronal cell death and mitochondrial dysfunction. Our results indicate that endogenous Ngb expression may be upregulated by low dose Aβ25-35, which is responsible for protecting against Aβ25-35-mediated neurotoxicity. These experimental findings suggest that upregulation of endogenous Ngb expression might be an effective intervention approach for AD.

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