Cited by 630Cell death mechanisms and regulationFerroptosis and cancer prognosisDeath, Funerary Practices, and Mourning

Regulated necrosis: disease relevance and therapeutic opportunities

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Conrad, Marcus, Angeli, José Pedro Friedmann, Vandenabeele, Peter, Stockwell, Brent R.·2016·Nature Reviews Drug Discovery

Abstract

The discovery of regulated cell death presents tantalizing possibilities for gaining control over the life-death decisions made by cells in disease. Although apoptosis has been the focus of drug discovery for many years, recent research has identified regulatory mechanisms and signalling pathways for previously unrecognized, regulated necrotic cell death routines. Distinct critical nodes have been characterized for some of these alternative cell death routines, whereas other cell death routines are just beginning to be unravelled. In this Review, we describe forms of regulated necrotic cell death, including necroptosis, the emerging cell death modality of ferroptosis (and the related oxytosis) and the less well comprehended parthanatos and cyclophilin D-mediated necrosis. We focus on small molecules, proteins and pathways that can induce and inhibit these non-apoptotic forms of cell death, and discuss strategies for translating this understanding into new therapeutics for certain disease contexts.

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  1. [187]US National Library of Medicine. ClinicalTrials.gov [ online], https://clinicaltrials.gov/ct2/show/NCT00271765?term=NCT00271765&rank=1 (2006). 28792816
  2. [188]US National Library of Medicine. ClinicalTrials.gov [ online], https://clinicaltrials.gov/ct2/show/NCT00271167 (2005). 28792816

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Authors
Conrad, M., Angeli, J. P. F., Vandenabeele, P., & Stockwell, B. R.
Affiliations
  • Helmholtz Munich (DE)
  • Vlaams Instituut voor Biotechnologie (BE)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Conrad, Marcus
  • Vandenabeele, Peter
  • Stockwell, Brent R.
Venue
Nature Reviews Drug Discovery
Published
2016-01-18
Volume
15
Issue
5
Pages
348-366
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
OpenAlex
W2291832556
Cited by
630
References
197
Citations by year
2026: 31 · 2025: 54 · 2024: 58 · 2023: 64 · 2022: 85 · 2021: 65 · 2020: 54 · 2019: 66 · 2018: 60 · 2017: 68 · 2016: 25
FWCI
6.61
Type
journal article
Language
en
Open access
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • Site cant be reached (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders
  • National Science Foundation (0840451)
  • New York State Stem Cell Science
  • Deutsche Forschungsgemeinschaft (CO 291/5-1, CO 291/5, 291/2-3, CO 291/2‐3)
  • Fonds Wetenschappelijk Onderzoek (G.0875.11, G0C3114N, FWO G.0172.12, G.0172.12, KAN 31528711, FWO G.0875.11, G.0A45.12)
  • Universiteit Gent (01M00709)
  • Vlaams Instituut voor Biotechnologie (BOF09/01M00709)
  • Vlaamse regering (BOF09/01M00709)
  • Fondation contre le Cancer (2012-188)
  • National Institutes of Health
  • Helmholtz Zentrum München
  • National Cancer Institute (R35CA209896, R01CA097061, R21CA177591, R01CA161061)
  • National Center for Research Resources (S10RR025431)
  • Division of Chemistry
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
  • Social Sciences › Anthropology › Death, Funerary Practices, and Mourning
Keywords
regulated necrosis, necroptosis, ferroptosis, oxytosis, parthanatos, non-apoptotic cell death
MeSH terms
Animals, Disease, Humans, Necrosis, Signal Transduction, Small Molecule Libraries, Molecular Targeted Therapy

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