Prostaglandin J2: a potential target for halting inflammation-induced neurodegeneration

摘要: Prostaglandins (PGs) are produced via cyclooxygenases, which enzymes that play a major role in neuroinflammation. Epidemiological studies show chronic treatment with low levels of cyclooxygenase inhibitors (nonsteroidal anti-inflammatory drugs (NSAIDs)) lowers the risk for Alzheimer's disease (AD) and Parkinson's (PD) by as much 50%. Unfortunately, inhibiting cyclooxygenases NSAIDs blocks synthesis downstream neuroprotective neurotoxic PGs, thus producing adverse side effects. We focus on prostaglandin J2 (PGJ2) because it is highly compared to PGA1, D2, E2. Unlike other PGJ2 its metabolites have cyclopentenone ring reactive α,β-unsaturated carbonyl groups form covalent Michael adducts key cysteines proteins GSH. Cysteine-binding electrophiles such considered an important determining whether neurons will live or die. discuss vitro vivo showing induces pathological processes relevant neurodegenerative disorders AD PD. Further, we our work increasing intracellular cAMP lipophilic peptide PACAP27 counteracts some PGJ2-induced detrimental New therapeutic strategies neutralize effects specific PGs from could significant impact fewer