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Regulated necrosis: Disease relevance and therapeutic opportunities.
Nat. Rev. Drug Discov. 15, 348-366 (2016)
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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Publication type
Article: Journal article
Document type
Review
Keywords
Mitochondrial Permeability Transition; Glutathione-peroxidase 4; Nonapoptotic Cell-death; Mixed Lineage Kinase; Small-molecule Inhibitor; Domain-like Protein; Nlrp3 Inflammasome Activation; Alpha-dependent Apoptosis; Transient Focal Ischemia; Kappa-b Activation
ISSN (print) / ISBN
1474-1776
Journal
Nature Reviews - Drug Discovery
Quellenangaben
Volume: 15,
Issue: 5,
Pages: 348-366
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)