title: Cyclooxygenase-dependent lipid-modification of brain proteins.
abstract: Substantial evidence indicates that both beta-amyloid and cyclooxygenase activity contribute to the pathogenesis of Alzheimer disease. The immediate product of the cyclooxygenases, prostaglandin H2, rapidly rearranges in aqueous solution, with approximately 20% being converted to levuglandins E2 and D2. These gamma-ketoaldehydes are highly reactive and rapidly adduct to accessible amine groups on macromolecules, particularly the epsilon-amine of lysine residues on proteins. The immediate LG-lysine adducts are themselves reactive, and can covalently crosslink proteins. PGH2, acting via LGs, accelerates the formation of the type of oligomers of amyloid beta that has been associated with neurotoxicity. In this review, we discuss the cyclooxygenase-dependent lipid-modification of proteins by levuglandins in vitro, in cells in culture and in vivo in transgenic mice over-expressing COX in the brain.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602, USA. olivier.boutaud@vanderbilt.edu
authors.forename: Olivier
authors.initials: O
authors.lastname: Boutaud
authors.forename: Katrin I
authors.initials: KI
authors.lastname: Andreasson
authors.forename: Irène
authors.initials: I
authors.lastname: Zagol-Ikapitte
authors.forename: John A
authors.initials: JA
authors.lastname: Oates
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D011458:Prostaglandins E; D011451:Prostaglandin-Endoperoxide Synthases