Necroptosis: a crucial pathogenic mediator of human disease

Necroptosis is a genetically regulated form of necrotic cell death that has emerged as an important pathway in human disease. The necroptosis pathway is induced by a variety of signals, including death receptor ligands, and regulated by receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3)...

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Vydané v:JCI insight Ročník 4; číslo 15
Hlavní autori: Choi, Mary E., Price, David R., Ryter, Stefan W., Choi, Augustine M. K.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States American Society for Clinical Investigation 08.08.2019
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ISSN:2379-3708, 2379-3708
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Shrnutí:Necroptosis is a genetically regulated form of necrotic cell death that has emerged as an important pathway in human disease. The necroptosis pathway is induced by a variety of signals, including death receptor ligands, and regulated by receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), which form a regulatory necrosome complex. RIPK3-mediated phosphorylation of MLKL executes necroptosis. Recent studies, using animal models of tissue injury, have revealed that RIPK3 and MLKL are key effectors of injury propagation. This Review explores the functional roles of RIPK3 and MLKL as crucial pathogenic determinants and markers of disease progression and severity in experimental models of human disease, including acute and chronic pulmonary diseases; renal, hepatic, cardiovascular, and neurodegenerative diseases; cancer; and critical illness.
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SourceType-Scholarly Journals-1
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ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.128834