Antagonism of Neuronal Prostaglandin E-2 Receptor Subtype 1 Mitigates Amyloid beta Neurotoxicity In Vitro

作者：Li Xianwu^*; Rose Shannon E; Montine Kathleen S; Keene C Dirk; Montine Thomas J

来源：Journal of Neuroimmune Pharmacology, 2013, 8(1): 87-93.

DOI：10.1007/s11481-012-9380-1

• Prostaglandin E2
• Amyloid beta
• Alzheimer's disease

Multiple lines of evidence indicate that regional brain eicosanoid signaling is important in initiation and progression of neurodegenerative conditions that have neuroinflammatory pathologic component, such as AD. We hypothesized that PGE(2) receptor subtype 1 (EP1) signaling (linked to intracellular Ca2+ release) regulates A beta peptide neurotoxicity and tested this in two complementary in vitro models: a human neuroblastoma cell line (MC65) producing A beta(1-40) through conditional expression of the APP C-terminal portion, and murine primary cortical neuron cultures exposed to A beta(1-42). In MC65 cells, EP1 receptor antagonist SC-51089 reduced A beta neurotoxicity similar to 50 % without altering high molecular weight A beta immunoreactive species formation. Inositol-3-phosphate receptor antagonist 2-aminoethoxy-diphenyl borate offered similar protection. SC-51089 largely protected the neuron cultures from synthetic A beta(1-42) neurotoxicity. Nimodipine, a Ca2+ channel blocker, was completely neuroprotective in both models. Based on these data, we conclude that suppressing neuronal EP1 signaling may represent a promising therapeutic approach to ameliorate A beta peptide neurotoxicity.

• 出版日期2013-3