NADPH oxidase mediates -amyloid peptide-induced activation of ERK in hippocampal organotypic cultures

Background: Previous studies have shown that beta amyloid (A) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signal-regulated kinase (ERK) cascade. In this study we sought to characterize the cellular localization of phosphorylated, active ERK in organotypic hippocampal cultures after acute exposure to either A (1-42) or nicotine. Results. We observed that A and nicotine increased the levels of active ERK in distinct cellular localizations. We also examined whether phospho-ERK was regulated by redox signaling mechanisms and found that increases in active ERK induced by A and nicotine were blocked by inhibitors of NADPH oxidase. Conclusion. Our findings indicate that NADPH oxidase-dependent redox signaling is required for A-induced activation of ERK, and suggest a similar mechanism may occur during early stages of Alzheimer's disease.