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Microglial phagocytosis of neurons in neurological disease

      Synaptic and/or neuronal loss occurs with neuroinflammation in multiple brain pathologies. Microglia are brain phagocytes and we find that activated microglia can phagocytose live neurons in a variety of conditions. Stressed-but-viable neurons exposed the ‘eat-me’ signal phosphatidylserine, which induced phagocytosis via the opsonin MFG-E8 and phagocytic vitronectin receptor (VNR) on microglia. Activated microglia released galectin-3 that opsonised desialylated neurons for phagocytosis via the MerTK receptor. UDP release from neurons induced engulfment via the P2Y6 receptor. Inflammatory activation of neuronal-glial co-cultures, by nanomolar β-amyloid, LPS, TNFα or rotenone, resulted in progressive loss of neurons and synapses (without any apoptosis or necrosis), accompanied by microglial phagocytosis of neurons, and prevented by blocking phagocytic receptors.
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