A Bird’s Eye View of Necroptosis
Necroptosis is a type of regulated necrotic death driven by defined molecular pathways. Regulated necrosis regulates programmed cell death. Necroptosis is at the center of the pathophysiology of several clinically-relevant disease states, including myocardial infarction and stroke, atherosclerosis, ischemia-reperfusion injury, pancreatitis, and inflammatory bowel disease. Necroptosis results in necrosis-like morphological changes, such as cell swelling, plasma membrane pore formation, and membrane rupture. It also requires co-activation of receptor-interacting protein (RIP) 1 and RIP3 kinases. Necrosome is a complex formed by RIP1, RIP3 and Fas-associated proteins with death domain (FADD). Several studies in the preclinical stage have demonstrated that targeting necrosome can have variable effects on progression of tumors, indicating that it is largely cell-type or context dependent.