• caspase-3;
  • cortical neurons;
  • cytochrome c;
  • FK506;
  • mitochondrial dysfunction;
  • rat


It is usually accepted that prion and amyloid-beta (Aβ) peptides induce apoptotic cell death. However, the mechanisms that trigger neuronal death, induced by these amyloidogenic peptides, remain to be clarified. In the present study we analysed the neurotoxic effects of the synthetic prion and Aβ peptides, PrP106-126 and Aβ25−35, in primary cultures of rat brain cortical cells. PrP106-126 and Aβ25−35 incubated at a concentration of 25 µm for 24 h, did not affect cell membrane integrity, but decreased the metabolic capacity of the cells. The intracellular free Ca2+ concentration and reactive oxygen species levels increased significantly after 24 h treatment with PrP106-126 and Aβ25−35. Furthermore, these peptides (after 24 h exposure) also induced cytochrome c release from mitochondria and increased caspase-3-like activity. FK506, an inhibitor of the Ca2+/calmodulin-dependent phosphatase, calcineurin, was able to prevent cytochrome c release, caspase-3 activation and cell death induced by Aβ25−35 or PrP106-126 peptides. Taken together these data suggest that calcineurin is involved in Aβ25−35 and PrP106-126 neurotoxicity.