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Necroptosis: a novel way of regulated necrosis with large pathophysiological implications

Peter Vandenabeele (UGent) , Tom Vanden Berghe (UGent) and Nozomi Takahashi (UGent)
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Abstract
Necrosis is a histopathologic term but also refers to a cell death process that was generally considered as accidental due to physicochemical injury. Necrosis is characterized by swelling of the cell (oncosis), plasma membrane rupture, and release of intracellular content. Recently, a regulated form of necrosis has been identified, termed necroptosis, in which receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) proteins play a crucial role through the formation of the so-called necrosome complex. Genetic ablation of these genes and the development of RIPK1 inhibitors, the so-called necrostatins, demonstrated that necroptosis can be targeted and suggest that it may play a crucial role in many different important inflammatory, infectious, and trauma-related disorders such as inflammatory graft rejection, cardiac infarction and brain trauma, acute pancreatitis, inflammatory bowel disease, ophthalmologic diseases, skin inflammation, systemic inflammatory response syndrome, atherosclerosis, and viral infection. However, in view of the pleiotropic role of RIPK1, RIPK3, and MLKL, it is also conceivable that other processes such as inflammasome formation are cotargeted in vivo, leading to the spectacular protective effects.

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Chicago
Vandenabeele, Peter, Tom Vanden Berghe, and Nozomi Takahashi. 2014. “Necroptosis: a Novel Way of Regulated Necrosis with Large Pathophysiological Implications.” In Pathobiology of Human Disease : a Dynamic Encyclopedia of Disease Mechanisms, ed. Linda M McManus and Richard N Mitchell, 153–161. Amsterdam, The Netherlands: Elsevier Academic Press.
APA
Vandenabeele, P., Vanden Berghe, T., & Takahashi, N. (2014). Necroptosis: a novel way of regulated necrosis with large pathophysiological implications. In L. M. McManus & R. N. Mitchell (Eds.), Pathobiology of human disease : a dynamic encyclopedia of disease mechanisms (pp. 153–161). Amsterdam, The Netherlands: Elsevier Academic Press.
Vancouver
1.
Vandenabeele P, Vanden Berghe T, Takahashi N. Necroptosis: a novel way of regulated necrosis with large pathophysiological implications. In: McManus LM, Mitchell RN, editors. Pathobiology of human disease : a dynamic encyclopedia of disease mechanisms. Amsterdam, The Netherlands: Elsevier Academic Press; 2014. p. 153–61.
MLA
Vandenabeele, Peter, Tom Vanden Berghe, and Nozomi Takahashi. “Necroptosis: a Novel Way of Regulated Necrosis with Large Pathophysiological Implications.” Pathobiology of Human Disease : a Dynamic Encyclopedia of Disease Mechanisms. Ed. Linda M McManus & Richard N Mitchell. Amsterdam, The Netherlands: Elsevier Academic Press, 2014. 153–161. Print.
@incollection{5889176,
  abstract     = {Necrosis is a histopathologic term but also refers to a cell death process that was generally considered as accidental due to physicochemical injury. Necrosis is characterized by swelling of the cell (oncosis), plasma membrane rupture, and release of intracellular content. Recently, a regulated form of necrosis has been identified, termed necroptosis, in which receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) proteins play a crucial role through the formation of the so-called necrosome complex. Genetic ablation of these genes and the development of RIPK1 inhibitors, the so-called necrostatins, demonstrated that necroptosis can be targeted and suggest that it may play a crucial role in many different important inflammatory, infectious, and trauma-related disorders such as inflammatory graft rejection, cardiac infarction and brain trauma, acute pancreatitis, inflammatory bowel disease, ophthalmologic diseases, skin inflammation, systemic inflammatory response syndrome, atherosclerosis, and viral infection. However, in view of the pleiotropic role of RIPK1, RIPK3, and MLKL, it is also conceivable that other processes such as inflammasome formation are cotargeted in vivo, leading to the spectacular protective effects.},
  author       = {Vandenabeele, Peter and Vanden Berghe, Tom and Takahashi, Nozomi},
  booktitle    = {Pathobiology of human disease : a dynamic encyclopedia of disease mechanisms},
  editor       = {McManus, Linda M and Mitchell, Richard N},
  isbn         = {9780123864574},
  language     = {eng},
  pages        = {153--161},
  publisher    = {Elsevier Academic Press},
  title        = {Necroptosis: a novel way of regulated necrosis with large pathophysiological implications},
  url          = {http://dx.doi.org/10.1016/B978-0-12-386456-7.01412-X},
  year         = {2014},
}

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