The role of necroptosis in disease and treatment. Issue 4 (20th December 2021)

• Record Type: Journal Article
• Authors: Liu, Xiaoxiao; Xie, Xin; Ren, Yuanyuan; Shao, Zhiying; Zhang, Nie; Li, Liantao; Ding, Xin; Zhang, Longzhen
• Is Part Of: MedComm. Volume 2:Issue 4(2022)
• Page Start: 730
• Page End: 755
• Publication Date: 2021-12-20
• Subjects: disease model -- inhibitor -- MLKL -- Necroptosis -- RIPK1 -- RIPK3; 610
• DOI: 10.1002/mco2.108
• Languages: English
• ISSNs: 2688-2663

Abstract

Abstract: Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor‐interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain‐like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this review, we attempt to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators including small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of various diseases. Abstract : Necroptosis is activated by a unique caspase‐independent signaling pathway and mainly relies on RIPK1/RIPK3/MLKL complex. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this article, we attempt to explore therapeutic prospects of the necroptosis regulators in health maintenance and disease treatment by describing the molecular mechanism of necroptosis and the role it played in disease and tissue homeostasis, summarizing the research and clinical applications of corresponding inhibitors and inducers which include small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of a variety of diseases including cancer, inflammation, infection, ischemia‐reperfusion injury, neurodegenerative diseases in various organs including cardiovascular, pulmonary, liver, pancreatic, renal, enteric, ocular, joint, and skin.