NF-κB is a nuclear transcription factor involved in the control of fundamental cellular functions including regulation of cell survival. We investigated NF-κB activation induced by two opposing modulators of cell viability: IL-1β and glutamate. We found that IL-1β activated p50, p65 and c-Rel subunits of NF-κB, while glutamate activated only p50 and p65 proteins. Cell stimulation by glutamate, correlated with expression of the pro-apoptotic genes Caspase-3, Caspase-2L and Bax. Conversely, IL-1β induced the expression of the short anti-apoptotic isoform of Caspase-2. Finally, we analysed the effect of the inhibition of IκBα degradation on glutamate-induced toxicity by using BAY 11-7082, a selective inhibitor of IκBα phosphorylation. Our results suggest that BAY 11-7082 preserves neuron viability from the glutamate-mediated injury.