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Hadian, K. ; Stockwell, B.R.*

The therapeutic potential of targeting regulated non-apoptotic cell death.

Nat. Rev. Drug Discov. 22, 723-742 (2023)
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Cell death is critical for the development and homeostasis of almost all multicellular organisms. Moreover, its dysregulation leads to diverse disease states. Historically, apoptosis was thought to be the major regulated cell death pathway, whereas necrosis was considered to be an unregulated form of cell death. However, research in recent decades has uncovered several forms of regulated necrosis that are implicated in degenerative diseases, inflammatory conditions and cancer. The growing insight into these regulated, non-apoptotic cell death pathways has opened new avenues for therapeutic targeting. Here, we describe the regulatory pathways of necroptosis, pyroptosis, parthanatos, ferroptosis, cuproptosis, lysozincrosis and disulfidptosis. We discuss small-molecule inhibitors of the pathways and prospects for future drug discovery. Together, the complex mechanisms governing these pathways offer strategies to develop therapeutics that control non-apoptotic cell death.
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Publication type Article: Journal article
Document type Review
Keywords Mixed Lineage Kinase; Poly(adp-ribose) Par Polymer; Interacting Protein-1 Rip1; Glutathione-peroxidase 4; Gamma-inducing Factor; Highly Potent; Nlrp3 Inflammasome; Domain-like; Lipid-peroxidation; Cognitive Impairment
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1474-1776
Journal Nature Reviews - Drug Discovery
Quellenangaben Volume: 22, Issue: 9, Pages: 723-742 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-509800-003
Grants NINDS
NCI grant
DOI 10.1038/s41573-023-00749-8
WOS ID 001044193400001
Scopus ID 85166943169
PubMed ID 37550363
Erfassungsdatum 2023-10-06
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