Abstract
Regulated cell death has essential functions in development and in adult tissue homeostasis. Necroptosis is a newly discovered pathway of regulated necrosis that requires the proteins RIPK3 and MLKL and is induced by death receptors, interferons, toll-like receptors, intracellular RNA and DNA sensors, and probably other mediators. RIPK1 has important kinase-dependent and scaffolding functions that inhibit or trigger necroptosis and apoptosis. Mouse-model studies have revealed important functions for necroptosis in inflammation and suggested that it could be implicated in the pathogenesis of many human inflammatory diseases. We discuss the mechanisms regulating necroptosis and its potential role in inflammation and disease.
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Acknowledgements
We apologise to all the authors whose work we could not cite in this Review due to space limitations. M.P. acknowledges funding from the European Research Council (2012-ADG_20120314), the German Research Foundation (SFB670, SFB829, SPP1656), the European Commission (Grants 223404 (Masterswitch) and 223151 (InflaCare)), the Deutsche Krebshilfe, the Else Kröner-Fresenius-Stiftung and the Helmholtz Alliance (PCCC). Research in the Vandenabeele unit is supported by Belgian grants (Interuniversity Attraction Poles, IAP 7/32), Flemish grants (Research Foundation Flanders, FWO G.0875.11, FWO G.0973.11 N, FWO G.0A45.12 N, FWO G.0172.12, FWO G.0787.13N, G0C3114N, FWO KAN 31528711 and Foundation against Cancer 2012-188), Gent University grants (MRP, GROUP-ID consortium) and grants from Flanders Institute for Biotechnology (VIB). P.V. holds a Methusalem grant (BOF09/01M00709) from the Flemish Government.
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Pasparakis, M., Vandenabeele, P. Necroptosis and its role in inflammation. Nature 517, 311–320 (2015). https://doi.org/10.1038/nature14191
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DOI: https://doi.org/10.1038/nature14191
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