The role of calcineurin in amyloid-β-peptides-mediated cell death

Amyloid beta-peptide (A beta) is widely held to be associated with Alzheimer's disease. It was previously demonstrated by our group that A beta induces cell death by an apoptotic process. We report here that activation of the caspase-3 apoptotic cascade is regulated by calcineurin-mediated BAD dephosphorylation. Calcineurin inhibitors were also proven to be effective by preventing the loss of mitochondrial membrane potential (Delta Psi m) induced by A beta, not allowing cytochrome c release from mitochondria and subsequently caspase-3 activation. Considering the results presented, we argue that calcineurin activation and BAD dephosphorylation are upstream in premitochondrial signaling events leading to caspase-3 activation in A beta-peptide-treated cells. (C) 2005 Elsevier B.V. All rights reserved.