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. 2006 Apr 5;15(2):134–138. doi: 10.1111/j.1750-3639.2005.tb00509.x

Microglial EP2 as a New Target to Increase Amyloid β Phagocytosis and Decrease Amyloid β‐Induced Damage to Neurons

Feng‐Shiun Shie 1, Kathleen S Montine 1, Richard M Breyer 2, Thomas J Montine 1,✉
PMCID: PMC8095884  PMID: 15912885

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 Aβ1–42 coupled with enhanced phagocytosis of Aβ 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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