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Microglial EP2 as a new target to increase amyloid beta phagocytosis and decrease amyloid beta-induced damage to neurons.

Feng-Shiun Shie·Kathleen S Montine·Richard M Breyer·Thomas J Montine
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Abstract

Epidemiologic and animal model data support a role for the prostaglandin pathway in AD pathogenesis. However, unexpected toxicity from protracted use of some nonsteroidal anti-inflammatory drugs (NSAIDs) compels investigation of therapeutic targets in this pathway other than COX inhibitors. Previously, we have shown that mice lacking one specific receptor for PGE2, EP2 (EP2-/-), are protected from the indirect neurotoxic effects of cerebral innate immune response mediated by CD14-dependent activation. Here we review data showing that EP2-/- microglia have a highly desirable combination of features: ablated indirect neurotoxicity following exposure to Abeta(1-42) coupled with enhanced phagocytosis of Abeta peptides, both synthetic and those deposited in human brain. These data point to microglial EP2 as a more focused target within the PG pathway for therapy in AD.

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Alzheimer DiseaseAmyloid beta-PeptidesAnimalsAnti-Inflammatory Agents, Non-SteroidalBrainHumansLipopolysaccharide ReceptorsMiceMicrogliaNeuronsPhagocytosisReceptors, Prostaglandin EJournal ArticleReview

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Feng-Shiun Shie, Kathleen S Montine, Richard M Breyer, Thomas J Montine. 2005. Microglial EP2 as a new target to increase amyloid beta phagocytosis and decrease amyloid beta-induced damage to neurons.. https://doi.org/10.1111/j.1750-3639.2005.tb00509.x

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