Knockout of P2Y12 receptor facilitates neuronal envelopment by reactive microglia and accelerates prion disease

This study redefines P2Y12 not as a passive marker of homeostasis but as an active regulator of neuroimmune dynamics. We demonstrate that P2Y12 is essential for maintaining balanced microglia-neuron communication under physiological conditions and for restraining maladaptive microglial behavior during chronic neurodegeneration associated with prion disease. These findings uncover a novel mechanism by which microglia contribute to disease progression and position P2Y12 as a potential therapeutic target for modulating microglial responses in neurodegenerative disorders.