Cyclooxygenase-Dependent Lipid-Modification of Brain Proteins

Abstract
Substantial evidence indicates that both β-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 y-ketoaldehydes are highly reactive and rapidly adduct to accessible amine groups on macromolecules, particularly the ɛ-amine of lysine residues on proteins. The immediate LG-lysine ad-ducts are themselves reactive, and can covalently crosslink proteins. PGH2, acting via LGs, accelerates the formation of the type of oligomers of amyloid β 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.

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