Curing the incurable – targeting necrotic cell death

Necrosisis, the main mode of cell death, is involved in many clinical conditions, which affect hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering drug development. We identified key proteolytic enzymes essential for necrosis, using a combination of chemical, biochemical, enzymology and screening approaches. These findings enable breakthrough strategies to treat and prevent necrosis, including known medicines used for other indications, siRNAs, and establishing a platform for design of new inhibitory molecules. Indeed, inhibitors of these enzymes demonstrated protective activity in-vitro and in-vivo in animal models of traumatic brain injury, acute myocardial infarction and drug-induced liver toxicity. Consequently, this study may pave the way for the development of novel therapies for the treatment, inhibition or prevention of a large number of untreatable diseases.