Caspase-3 activation by β-amyloid and prion protein peptides is independent from their neurotoxic effect

Abstract

Synthetic peptides corresponding to residues 25–35 of β-amyloid (β 25–35) and 106–126 of prion protein (PrP 106–126) are amyloidogenic and cause neuronal death by apoptosis in vitro. We evaluated, in rat cortical neurons, the role of caspases activation in the peptides neurotoxicity by measuring of caspase-3 (CPP32) activity and applying a non-selective caspase inhibitor (z-VAD-fmk) or CPP32-specific inhibitor (Asp-Glu-Val-Asp-CHO (DEVD-CHO)). CPP32 was dose-dependently activated by both peptides (2.5–50 μM). The caspase inhibitors completely abolished the CPP32 activation induced by the peptides. However, the neurotoxic effect was partially attenuated with z-VAD-fmk, while no antagonism was found with DEVD-CHO. Thus, although β 25–35 and PrP 106–126 robustly activated CPP32, their neurotoxic effect was independent of this caspase activation.