Caspase inhibitors protect neurons by enabling selective necroptosis of inflamed microglia

Background: Caspase-8 signaling can mediate apoptosis or survival depending on the cellular context. Results: Inflamed microglia survive because of caspase-dependent suppression of RIPK1-mediated necroptosis for survival. Conclusion: Caspase inhibition rescues neurons by triggering necroptosis of neurotoxic inflamed microglia. Significance: We demonstrate a novel neuroprotective mechanism of caspase inhibitors, namely killing of neurotoxicmicroglia by necroptosis.