Necroptosis: A crucial pathogenic mediator of human disease Report uri icon

Overview

MeSH Major

  • Autophagy
  • Cecum
  • Disease Models, Animal
  • Sepsis

abstract

  • © 2019 American Society for Clinical Investigation. Necroptosis is a genetically regulated form of necrotic cell death that has emerged as an important pathway in human disease. The necroptosis pathway is induced by a variety of signals, including death receptor ligands, and regulated by receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), which form a regulatory necrosome complex. RIPK3-mediated phosphorylation of MLKL executes necroptosis. Recent studies, using animal models of tissue injury, have revealed that RIPK3 and MLKL are key effectors of injury propagation. This Review explores the functional roles of RIPK3 and MLKL as crucial pathogenic determinants and markers of disease progression and severity in experimental models of human disease, including acute and chronic pulmonary diseases; renal, hepatic, cardiovascular, and neurodegenerative diseases; cancer; and critical illness.

publication date

  • August 8, 2019

Research

keywords

  • Report

Identity

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.128834

Additional Document Info

volume

  • 4

number

  • 15