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It is mediated by specific signaling molecules, notably, including receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) and mixed lineage kinase domain-like protein (MLKL), which drive necroptosis by activating related signaling pathways in response to severe stress or pathological stimuli ( TNF- is the primary upstream mediator of in necroptosis (Newton and Manning, 2016)