The role of platelet activating factor in prion and amyloid-β neurotoxicity

In the priori diseases, neurodegeneration is preceded by the accumulation of the disease-associated isoform of the prion protein (PrP^d). In the present study, neurones treated with three different phospholipase A ₂ inhibitors were resistant to the toxic effects of PrP peptides or a synthetic miniprion (sPrP106). Phospholipase A₂ inhibitors also protected neurones against a toxic peptide found in Alzheimer's disease (amyloid-β_1-42). Further studies showed that neurones pre-treated with platelet activating factor (PAF) antagonists were equally resistant to PrP peptides or amyloid-β_1-42. Moreover, both phospholipase A₂ inhibitors and PAF antagonists reduced the activation of caspase-3, a marker of apoptosis, and the production of prostaglandin E₂ that is closely associated with neuronal death in prion or Alzheimer's diseases.