Necroptosis
Necroptosis also known as programmed necrosis is a mechanism that regulates cell death. Necrotic cell death has been considered a form of passive cell death. However, the discovery that TNFalpha mediated necrosis can be inhibited by a specific inhibitor of RIP1 kinase, necrostatin-1, led to the concept of necroptosis [1];[2]. Necroptosis has now been established as a regulated necrotic cell death pathway by RIP1 and RIP3 kinases.[3]
Under conditions that are insufficient to trigger apoptosis, TNFα activates TNFR1 and in turn induces recruitment of RIP1 kinase and other proteins to form complex I. Subsequently, these proteins dissociate from TNFR1 and RIP1 can be found in the cytosol in complex IIb, which includes RIP1, RIP3, caspase 8 and FADD. The formation of complex IIb leads to necroptosis.[3]
Necroptosis plays a role in various pathological forms of cell death, including ischemic brain injury, neurodegenerative diseases and viral infections.[4]
References
- ^ Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J (2005). "Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury". Nat Chem Biol. 1 (2): 112–9. PMID 16408008.
{{cite journal}}: Cite has empty unknown parameter:|1=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008). "Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury". Nat Chem Biol. 4 (5): 313–21. PMID 18408713.
{{cite journal}}: Text "doi: 10.1038/nchembio.83" ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Christofferson DE, Yuan J (2010). "Necroptosis as an alternative form of programmed cell death". Curr. Opin. Cell Biol. 22 (2): 263–8. doi:10.1016/j.ceb.2009.12.003. PMC 2854308. PMID 20045303.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Dunai, Z (2011). "Necroptosis: biochemical, physiological and pathological aspects". Pathol. Oncol. Res.: POR. 17 (4): 791–800. PMID 21773880.
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