Regulated necrosis: disease relevance and therapeutic opportunities
Open accessAbstract
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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Specific pharmacological inhibitors of PARP1 efficiently delay parthanatos in multiple cell types, in vitro and in vivo.
“specific pharmacological inhibitors of PARP1 efficiently delay parthanatos in multiple cell types, in vitro and in vivo [1, 669].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [1]
PARP1 inhibition by pharmacological or genetic interventions mediates robust cytoprotective effects in multiple animal models of disease.
“PARP1 inhibition by pharmacological or genetic interventions mediates robust cytoprotective effects in multiple animal models of disease [1, 669].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [1]
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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
- PMC
- PMC6531857
- 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
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- 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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