Necroptosis signaling in liver diseases: An update

Pharmacol Res. 2019 Oct:148:104439. doi: 10.1016/j.phrs.2019.104439. Epub 2019 Aug 30.

Abstract

The apoptosis alternate cell death pathways are extensively studied in recent years and their significance has been well recognized. With identification of newer cell death pathways, the therapeutic opportunities to modulate cell death have indeed further extended. Necroptosis, among other apoptosis alternate pathways, has been immensely studied recently in different hepatic disease models. Receptor-interacting protein 1 (RIPK1), RIPK3 and mixed lineage kinase domain like (MLKL) seemed to be the key players to mediate necroptosis pathway. Initially, necroptosis seemed to be following the typical pathway. But recently diverse pathways and outcomes have been observed. With recent studies reporting diverse outcomes, the necroptosis signalling has become a lot more interesting and intricate. The typical RIPK1 signalling followed by RIPK3 and MLKL might not always be strictly followed. Although, necroptosis signalling has been intensively investigated in various disease conditions; however, there is still a need to further elaborate and understand the unique scaffolding and kinase properties and other signalling interactions of necroptosis signalling molecules.

Keywords: MLKL; Necroptosis; RIPK3.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Liver Diseases / metabolism*
  • Necroptosis / physiology*
  • Protein Kinases / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / physiology*

Substances

  • Protein Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases