title: Prostaglandin H2 (PGH2) accelerates formation of amyloid beta1-42 oligomers.
abstract: Epidemiologic evidence implicates cyclooxygenase activity in the pathogenesis of Alzheimer's disease, in which amyloid plaques have been found to contain increased levels of dimers and higher multimers of the amyloid beta peptide. The product of the oxygenation of arachidonic acid by the cyclooxygenases, prostaglandin H2 (PGH2), rearranges non-enzymatically to several prostaglandins, including the highly reactive gamma-keto aldehydes, levuglandins E2 and D2. We demonstrate that PGH2 markedly accelerates the formation of dimers and higher oligomers of amyloid beta1-42. This is associated with the formation of levuglandin adducts of the peptide. These findings provide the molecular basis for a hypothesis linking cyclooxygenase activity to the formation of oligomers of amyloid beta.
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D002614:Chelating Agents / Q000737:chemistry; D019281:Dimerization; D004492:Edetic Acid / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry; D044262:Prostaglandin H2; D011458:Prostaglandins E / Q000737:chemistry; D011463:Prostaglandins H / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011108:Polymers; D011458:Prostaglandins E; D011463:Prostaglandins H; C075222:amyloid beta-protein (1-42); D044262:Prostaglandin H2; C047684:levuglandin E2; D004492:Edetic Acid