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Updated: Jan 15, 2026

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

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Necroptotic cell death consequences and disease relevance

James E Vince1,2, Nadia M Davidson3,4, Maria C Tanzer5,6

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. vince@wehi.edu.au.

Nature Immunology
|October 15, 2025
PubMed

Insights

Necroptosis, a programmed cell death pathway, is genetically encoded and implicated in human diseases. Targeting necroptosis may offer clinical benefits by preventing tissue damage and inflammation.

Area of Science:

  • Cellular Biology
  • Immunology
  • Pathology

Background:

  • Cell death research has revealed genetically encoded pathways beyond apoptosis.
  • Necrosis encompasses distinct modalities like pyroptosis, necroptosis, and ferroptosis.
  • Targeting cell death pathways offers potential therapeutic strategies for inflammatory diseases.

Purpose of the Study:

  • To review the evidence for targeting necroptosis, a specific form of programmed necrosis.
  • To examine the expression of necroptosis machinery in human organs and cell types.
  • To assess the role of necroptosis in human diseases and its therapeutic potential.

Main Methods:

  • Review of molecular, structural, and disease-relevant findings on necroptosis.
  • Identification of key molecular players (ZBP1, RIPK1, RIPK3, MLKL) in human necroptosis.
  • Analysis of immunogenic consequences and disease association of necroptosis.

Main Results:

  • A specific necroptotic signature involving ZBP1, RIPK1, RIPK3, and MLKL is identified in human lymphocytes.
  • Evidence suggests necroptosis is active in humans and can be triggered by ischemic injuries.
  • Mouse studies show limitations due to differences with the human necroptotic apparatus.

Conclusions:

  • Necroptosis is a distinct, genetically encoded cell death pathway with significant implications for human health.
  • Targeting necroptosis holds promise for treating inflammatory diseases and preventing tissue damage.
  • Further research is needed to overcome limitations in mouse models and fully elucidate necroptosis's clinical relevance.

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