title: Microglial EP2 as a new target to increase amyloid beta phagocytosis and decrease amyloid beta-induced damage to neurons.
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.
authors.affiliation: Department of Pathology, University of Washington, Seattle 98104, USA.
authors.forename: Feng-Shiun
authors.initials: FS
authors.lastname: Shie
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Montine
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001921:Brain / Q000473:pathology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D018078:Receptors, Prostaglandin E / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018950:Lipopolysaccharide Receptors; D018078:Receptors, Prostaglandin E