Integrated study of cell death: Biology focusing on multiple mechanisms of mammalian cell death

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Based on our hypothesis that non-apoptotic cell death mechanisms play an important role in physiological programmed death in addition to pathological death, we have performed detailed studies and discovered that non-apoptotic death mechanisms play the major role in programmed death involved in turn over of mouse small intestinal epithelial cells, placenta formation, and bone formation as well as in pathological death of neurons in INAD model mouse withmutations in PLA2G6 gene. This implies that cell death research needs the paradigm shift. We have also found some chemical inhibitors or genes for theabove-mentioned non-apoptotic programmed death and for non-apoptotic death,which we observed in cultured cells, providing the firm basis for the next generation of cell death research.