Necroptosis: a regulated inflammatory mode of cell death

J Neuroinflammation. 2018 Jul 6;15(1):199. doi: 10.1186/s12974-018-1235-0.


Programmed cell death has a vital role in embryonic development and tissue homeostasis. Necroptosis is an alternative mode of regulated cell death mimicking features of apoptosis and necrosis. Necroptosis requires protein RIPK3 (previously well recognized as regulator of inflammation, cell survival, and disease) and its substrate MLKL, the crucial players of this pathway. Necroptosis is induced by toll-like receptor, death receptor, interferon, and some other mediators. Shreds of evidence based on a mouse model reveals that deregulation of necroptosis has been found to be associated with pathological conditions like cancer, neurodegenerative diseases, and inflammatory diseases. In this timeline article, we are discussing the molecular mechanisms of necroptosis and its relevance to diseases.

Keywords: Inflammation; MLKL; Necroptosis; Neurodegenerative disease; RIPK3.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Humans
  • Inflammation* / genetics
  • Inflammation* / pathology
  • Inflammation* / physiopathology
  • Necrosis / pathology*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*


  • MLKL protein, human
  • Protein Kinases
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases