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

Shie FS, Montine KS, Breyer RM, Montine TJ
Brain Pathol. 2005 15 (2): 134-8

PMID: 15912885 · DOI:10.1111/j.1750-3639.2005.tb00509.x

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.

MeSH Terms (12)

Alzheimer Disease Amyloid beta-Peptides Animals Anti-Inflammatory Agents, Non-Steroidal Brain Humans Lipopolysaccharide Receptors Mice Microglia Neurons Phagocytosis Receptors, Prostaglandin E

Connections (1)

This publication is referenced by other Labnodes entities: