One of the mechanisms leading to neurodegeneration during Alzheimer's disease (AD) is amyloid β peptide neurotoxicity. In response to a variety of stress insults, namely oxidative stress, the transcription factor NF-kB can be activated. We have previously shown that amyloid β peptides 25-35 and 1-40 (Aβ 25-35 and Aβ 1-40) induces cell death. In response to Aβ 25-35 or 1-40 treatment, we observed an increase in superoxide dismutase (SOD) activity in NT2 cells. Amyloid beta peptides also induced an increase in SOD expression levels. This could result from NF-kB activation, as determined by the expression of p65. We observed that the NF-kB inhibitor, PDTC, prevented SOD overexpression after Aβ treatment. Previously we have shown that Aβ peptides could activate caspases-mediated apoptotic cell death. In this study, we analyzed if NF-kB activation prevented cells from caspases-activation and we also observed that inhibition of NF-kB by PDTC induced an increase in caspase-3 and caspase-6 activation. Taken together, these data suggest that pharmacological induction of NF-kB can be a potential target in Alzheimer's disease treatment.
Keywords: Alzheimer's Disease; Apoptosis; Aβ; Nf-kB.