Stimulation of PGE2 receptors EP2 and EP4 protects cultured neurons against oxidative stress and cell death following β‐amyloid exposure

• DOI: 10.1111/j.1460-9568.2005.04427.x
• Publication Date: 2005-11-01T13:56:58Z
• Authors: Valentina Echeverria; Andrew Clerman; Sylvain Doré
• Keywords: Prostaglandin E2 receptor

Alzheimer's disease (AD) is associated with gliosis, neuroinflammation and higher levels of prostaglandins. Conflicting roles for cyclooxygenases prostaglandins in the etiopathology AD have been reported. We hypothesized that PGE2 signaling through EP2 EP4 G-protein-coupled receptors could protect against amyloid beta-peptide (Abeta) neurotoxicity by increasing cAMP cascade. Using primary neuronal cultures, we investigated presence EP (EP1-4) action receptor agonists on susceptibility to Abeta1-42 toxicity. Low concentrations (1 microm) PGE2, butaprost (EP2 agonist), 1-hydroxy-PGE1 (EP4/EP3 agonist) were neuroprotective toxicity, while sulprostone (EP3/EP1 at similar doses had no detectable effects. receptor-mediated neuroprotection would involve changes levels, as both increased intracellular concentration approximately doubling basal exhibited actions Abeta-induced The protein kinase A (PKA) inhibitor RpcAMPS significantly attenuated butaprost, but not 1-hydroxy-PGE1, implying differences between protective mechanisms. Additionally, increase reactive oxygen species generated following exposure Abeta was reduced stimulation receptors. Together, these results indicate can neurons toxicity acting given stimulating a cascade events, including cAMP-PKA pathway. propose development testing specific downstream cyclooxygenase lead therapeutic applications.