Necroptosis

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The Necroptosis denotes a RIPK3-dependent regulated necrosis . Necroptosis is characterized by the activation of death receptors, for example the Fas receptor , as in apoptosis , but the cells subsequently initiate self-digestion, unlike in apoptosis. In various disease models, RIP3-deficient animals are therefore protected from diseases, e.g. B. in the context of ischemia / reperfusion damage, in TNF -mediated shock, in acute kidney failure induced by cisplatin , in chronic inflammatory bowel disease, in necrotizing pancreatitis and in the sepsis model . More recent results of a research group from the CECAD Cluster of Excellence led by Manolis Pasparakis also show that ligating the necroptosis could completely prevent an inflammatory skin disease, although apoptosis continued to take place in the cells. The prevention of necroptosis could therefore represent a new therapeutic approach for the treatment of inflammatory bowel and skin diseases. In addition, a team of scientists at the University of Zurich , led by Jean-Pierre Bourquin and Beat Bornhauser, recently developed a therapeutic approach for the treatment of acute lymphoblastic leukemia based on the activation of necroptosis.

literature

  • M. Dannappel, K. Vlantis et al. a .: RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. In: Nature. Volume 513, number 7516, September 2014, ISSN  1476-4687 , pp. 90-94, doi : 10.1038 / nature13608 , PMID 25132550 , PMC 4206266 (free full text).
  • A. Degterev, Z. Huang et al. a .: Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. In: Nature chemical biology. Volume 1, Number 2, July 2005, ISSN  1552-4450 , pp. 112-119, doi : 10.1038 / nchembio711 , PMID 16408008 .
  • S. McCom, J. Aguadé-Gorgorió et al. a .: Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL. In: Science Translational Medicine. May 18, 2016. doi : 10.1126 / scitranslmed.aad2986

Individual evidence

  1. ↑ a b Necroptosis - RIP3-dependent regulated necrosis. Clinic for kidney and hypertension diseases in Kiel.
  2. ↑ Thorsten Lieke: Necroptosis. In: Laborjournal 11, 2011.
  3. ↑ Enzyme stops cell death in the skin and intestines. DocCheck News, August 18, 2014.
  4. ^ University of Zurich - media release of May 18, 2016.