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Regulated necrosis: disease relevance and therapeutic opportunities

(2016) NATURE REVIEWS DRUG DISCOVERY. 15(5). p.348-366
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  • Methusalem Program
Abstract
The discovery of regulated cell death presents tantalizing possibilities for gaining control over the life-death decisions made by cells in disease. Although apoptosis has been the focus of drug discovery for many years, recent research has identified regulatory mechanisms and signalling pathways for previously unrecognized, regulated necrotic cell death routines. Distinct critical nodes have been characterized for some of these alternative cell death routines, whereas other cell death routines are just beginning to be unravelled. In this Review, we describe forms of regulated necrotic cell death, including necroptosis, the emerging cell death modality of ferroptosis (and the related oxytosis) and the less well comprehended parthanatos and cyclophilin D-mediated necrosis. We focus on small molecules, proteins and pathways that can induce and inhibit these non-apoptotic forms of cell death, and discuss strategies for translating this understanding into new therapeutics for certain disease contexts.
Keywords
MITOCHONDRIAL PERMEABILITY TRANSITION, GLUTATHIONE-PEROXIDASE 4, NONAPOPTOTIC CELL-DEATH, MIXED LINEAGE KINASE, SMALL-MOLECULE INHIBITOR, DOMAIN-LIKE PROTEIN, NLRP3 INFLAMMASOME ACTIVATION, ALPHA-DEPENDENT APOPTOSIS, TRANSIENT FOCAL ISCHEMIA, KAPPA-B ACTIVATION

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Citation

Please use this url to cite or link to this publication:

MLA
Conrad, Marcus et al. “Regulated Necrosis: Disease Relevance and Therapeutic Opportunities.” NATURE REVIEWS DRUG DISCOVERY 15.5 (2016): 348–366. Print.
APA
Conrad, M., Friedmann Angeli, J. P., Vandenabeele, P., & Stockwell, B. R. (2016). Regulated necrosis: disease relevance and therapeutic opportunities. NATURE REVIEWS DRUG DISCOVERY, 15(5), 348–366.
Chicago author-date
Conrad, Marcus, José Pedro Friedmann Angeli, Peter Vandenabeele, and Brent R Stockwell. 2016. “Regulated Necrosis: Disease Relevance and Therapeutic Opportunities.” Nature Reviews Drug Discovery 15 (5): 348–366.
Chicago author-date (all authors)
Conrad, Marcus, José Pedro Friedmann Angeli, Peter Vandenabeele, and Brent R Stockwell. 2016. “Regulated Necrosis: Disease Relevance and Therapeutic Opportunities.” Nature Reviews Drug Discovery 15 (5): 348–366.
Vancouver
1.
Conrad M, Friedmann Angeli JP, Vandenabeele P, Stockwell BR. Regulated necrosis: disease relevance and therapeutic opportunities. NATURE REVIEWS DRUG DISCOVERY. 2016;15(5):348–66.
IEEE
[1]
M. Conrad, J. P. Friedmann Angeli, P. Vandenabeele, and B. R. Stockwell, “Regulated necrosis: disease relevance and therapeutic opportunities,” NATURE REVIEWS DRUG DISCOVERY, vol. 15, no. 5, pp. 348–366, 2016.
@article{7236089,
  abstract     = {{The discovery of regulated cell death presents tantalizing possibilities for gaining control over the life-death decisions made by cells in disease. Although apoptosis has been the focus of drug discovery for many years, recent research has identified regulatory mechanisms and signalling pathways for previously unrecognized, regulated necrotic cell death routines. Distinct critical nodes have been characterized for some of these alternative cell death routines, whereas other cell death routines are just beginning to be unravelled. In this Review, we describe forms of regulated necrotic cell death, including necroptosis, the emerging cell death modality of ferroptosis (and the related oxytosis) and the less well comprehended parthanatos and cyclophilin D-mediated necrosis. We focus on small molecules, proteins and pathways that can induce and inhibit these non-apoptotic forms of cell death, and discuss strategies for translating this understanding into new therapeutics for certain disease contexts.}},
  author       = {{Conrad, Marcus and Friedmann Angeli, José Pedro and Vandenabeele, Peter and Stockwell, Brent R}},
  issn         = {{1474-1776}},
  journal      = {{NATURE REVIEWS DRUG DISCOVERY}},
  keywords     = {{MITOCHONDRIAL PERMEABILITY TRANSITION,GLUTATHIONE-PEROXIDASE 4,NONAPOPTOTIC CELL-DEATH,MIXED LINEAGE KINASE,SMALL-MOLECULE INHIBITOR,DOMAIN-LIKE PROTEIN,NLRP3 INFLAMMASOME ACTIVATION,ALPHA-DEPENDENT APOPTOSIS,TRANSIENT FOCAL ISCHEMIA,KAPPA-B ACTIVATION}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{348--366}},
  title        = {{Regulated necrosis: disease relevance and therapeutic opportunities}},
  url          = {{http://dx.doi.org/10.1038/nrd.2015.6}},
  volume       = {{15}},
  year         = {{2016}},
}

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