Amyloid-Beta(25-35) Upregulates Endogenous Neuroprotectant Neuroglobin Via Nf Kappa B 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 A beta(25-35), the neurotoxic fragment of A beta(1-40) and A beta(1-42), but was not further increased by a higher dose of A beta(25-35). Mutation analysis and supershift assay demonstrated that transcription factor Nuclear Factor kappa B (NF kappa B), kappa B2 and kappa B3 sites located in mouse Ngb promoter region were involved in dynamic regulation of Ngb expression in response to different doses of A beta(25-35) stimulation. In addition, we found that suppression of endogenous Ngb expression exacerbated A beta(2)(5-)(35)-induced neuronal cell death and mitochondrial dysfunction. Our results indicate that endogenous Ngb expression may be upregulated by low dose Ap beta(25-35), which is responsible for protecting against A beta(25-35)-mediated neurotoxicity. These experimental findings suggest that upregulation of endogenous Ngb expression might be an effective intervention approach for AD.