Silencing of the P2X7 receptor enhances amyloid-β phagocytosis by microglia

P2X7 receptor (P2X7R) is an ATP-gated cation channel that promotes microglia activation and plays a critical role in the pathogenesis of Alzheimer's disease. Inhibiting P2X7R indirectly reduces the rate of amyloid-β (Aβ)-induced neurodegeneration by suppressing secretion of inflammatory factors from activated microglia. We used RNA interference to silence P2X7R in microglial cells in vitro and found it markedly increased microglial phagocytosis of Aβ1-42. Increased phagocytic activity was dependent on decreasing the rate of interleukin-1β release from microglia and required inhibition of the COX-2 pathway. Modulation of microglial phagocytosis and secretion via silencing P2X7R may be a promising therapeutic option for the treatment of Alzheimer's disease.