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Regulated cell death has been recognized as a normal physiological process that functions to sculpt tissues during development and maintain tissue homeostasis by eliminating unnecessary or harmful cells.Cell death may occur through apoptosis or non-apoptotic cell death,such as necroptosis.Apoptosis is regulated by an evolutionarily conserved genetic program that includes members of Bcl-2 and caspase families.In early 1990s,we demonstrated that activation of caspases provides a key mechanism in mediating neuronal cell death during development as well as those induced by acute injury and chronic neurodegeneration.Apoptosis also plays a fundamental role in mediating DNA damage response by removing damaged cells.