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. Copyright (C) 2000 Elsevier Science Ireland Ltd.
- Alzheimer's disease
- Cortical culture
- Prion-related encephalopathies
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