Ab(25-35) peptide induces cell death in PC12 cells via mitochondrial damage and cytochrome c release

The pathological features of Alzheimer's disease include deposition of senile plaques in different brain zones formed by aggregates of fibrillar A? peptide (A?P), a neurotoxic metabolic product. In this study we used the soluble form of fragment 25-35 of A?P, that includes methionine 35, side chain of A?P, to investigate the role of redox state of Met-35 on the pathogenesis of AD, because this residue in A?P is the most susceptible to oxidation in vivo. The data obtained evidenced that A?(25-35) peptide determines a loss of PC12 cells viability determining mitochondrial damage with a possible trigger of pro-apoptotic signals. In particular, the following parameters were examined: cytochrome c release, mitochondrial membrane potential (??m) and mitochondrial respiration. In this study, three different peptides have been used: A?(25-35) with methionine 35 in the reduced state, oxidized to sulfoxide and/or substituted with norleucine. We conclude that alteration in the mitochondrial functionality might be a contributing factor to the pathogenesis of AD and the amplitude of the effects elicited by A? peptide is modulated by the redox state of methionine.