TY - JOUR
T1 - Necroptosis
T2 - A crucial pathogenic mediator of human disease
AU - Choi, Mary E.
AU - Price, David R.
AU - Ryter, Stefan W.
AU - Choi, Augustine M.K.
N1 - Funding Information:
This work was supported in part by NIH grants R01 HL132198, R01 HL133801, R01 HL055330 to MEC and AMKC; and NIH UL1 TR000457 to DRP.
Publisher Copyright:
© 2019 American Society for Clinical Investigation.
PY - 2019/8/8
Y1 - 2019/8/8
N2 - 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.
AB - 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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U2 - 10.1172/jci.insight.128834
DO - 10.1172/jci.insight.128834
M3 - Review article
C2 - 31391333
AN - SCOPUS:85071136789
SN - 2379-3708
VL - 4
JO - JCI insight
JF - JCI insight
IS - 15
M1 - e128834
ER -