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. 2006 Apr 5;15(2):139–142. doi: 10.1111/j.1750-3639.2005.tb00510.x

Cyclooxygenase‐Dependent Lipid‐Modification of Brain Proteins

Olivier Boutaud 1,✉, Katrin I Andreasson 3, Irène Zagol‐Ikapitte 1, John A Oates 1,2
PMCID: PMC8096006  PMID: 15912886

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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