The microglial P2Y₆ receptor mediates neuronal loss and memory deficits in neurodegeneration.

ABSTRACT: Microglia are implicated in neurodegeneration, potentially by phagocytosing neurons, but it is unclear how to block the detrimental effects of microglia while preserving their beneficial roles. The microglial P2Y₆ receptor (P2Y₆R) - activated by extracellular UDP released by stressed neurons - is required for microglial phagocytosis of neurons. We show here that injection of amyloid beta (Aβ) into mouse brain induces microglial phagocytosis of neurons, followed by neuronal and memory loss, and this is all prevented by knockout of P2Y₆R. In a chronic tau model of neurodegeneration (P301S TAU mice), P2Y₆R knockout prevented TAU-induced neuronal and memory loss. In vitro, P2Y₆R knockout blocked microglial phagocytosis of live but not dead

SUBMITTER: Puigdellivol M 

PROVIDER: S-EPMC8733854 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature