Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives

Version 1 : Received: 3 September 2020 / Approved: 4 September 2020 / Online: 4 September 2020 (07:21:17 CEST)

How to cite: Negroni, A.; Colantoni, E.; Cucchiara, S.; Stronati, L. Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives. Preprints 2020, 2020090084. https://doi.org/10.20944/preprints202009.0084.v1 Negroni, A.; Colantoni, E.; Cucchiara, S.; Stronati, L. Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives. Preprints 2020, 2020090084. https://doi.org/10.20944/preprints202009.0084.v1

Abstract

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Keywords

programmed cell death; inflammation; intestinal disease; cancer; inhibitors

Subject

Medicine and Pharmacology, Gastroenterology and Hepatology

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