The role of platelet activating factor in prion and amyloid-beta neurotoxicity.
In the prion diseases, neurodegeneration is preceded by the accumulation of the disease-associated isoform of the prion protein (PrP). In the present study, neurones treated with three different phospholipase A2 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-beta1-42). Further studies showed that neurones pre-treated with platelet activating factor (PAF) antagonists were equally resistant to PrP peptides or amyloid-beta1-42. 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.
Bate
Clive
C
Department of Veterinary Pathology, Glasgow University Veterinary School, Bearsden Road, Glasgow G61 1QH, UK. c.bate@vet.gla.ac.uk
Salmona
Mario
M
Williams
Alun
A
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D001932:Brain Neoplasms; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology*; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000633:toxicity*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000502:physiology*; D011328:Prions / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010972:Platelet Activating Factor; D011328:Prions; C075222:amyloid beta-protein (1-42); D010741:Phospholipases A; D054467:Phospholipases A2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015232:Dinoprostone