Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 73, Issue 11-12, Pages 2251-2267Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-016-2198-x
Keywords
Regulated necrosis; TNF; Programmed cell death; Ferroptosis; Necroptosis; Ferrostatins; Necrostatins
Categories
Funding
- National Institute of General Medical Sciences [R01GM080356, R01GM084205]
- German Research Foundation, Cluster of Excellence [EXC306]
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Interference with regulated necrosis for clinical purposes carries broad therapeutic relevance and, if successfully achieved, has a potential to revolutionize everyday clinical routine. Necrosis was interpreted as something that no clinician might ever be able to prevent due to the unregulated nature of this form of cell death. However, given our growing understanding of the existence of regulated forms of necrosis and the roles of key enzymes of these pathways, e.g., kinases, peroxidases, etc., the possibility emerges to identify efficient and selective small molecule inhibitors of pathologic necrosis. Here, we review the published literature on small molecule inhibition of regulated necrosis and provide an outlook on how combination therapy may be most effective in treatment of necrosis-associated clinical situations like stroke, myocardial infarction, sepsis, cancer and solid organ transplantation.
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