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Updated: Mar 27, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Regulated necrosis: disease relevance and therapeutic opportunities
Marcus Conrad1, José Pedro Friedmann Angeli1, Peter Vandenabeele2,3,4
1Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany.
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.
Insights
New regulated cell death pathways beyond apoptosis offer therapeutic targets. Understanding these non-apoptotic cell death routes, like necroptosis and ferroptosis, can lead to novel treatments for various diseases.
Area of Science:
- Cell Biology
- Molecular Medicine
- Drug Discovery
Background:
- Apoptosis has long been a focus for drug discovery in disease.
- Recent research uncovers regulated necrotic cell death pathways beyond apoptosis.
- These pathways offer new avenues for therapeutic intervention.
Purpose of the Study:
- To review emerging regulated necrotic cell death modalities.
- To highlight key molecules and pathways involved in these processes.
- To discuss therapeutic strategies for translating this knowledge into treatments.
Main Methods:
- Literature review of regulated necrotic cell death pathways.
- Analysis of small molecules, proteins, and signaling pathways.
- Discussion of therapeutic implications and strategies.
Main Results:
- Characterization of necroptosis, ferroptosis, oxytosis, parthanatos, and cyclophilin D-mediated necrosis.
- Identification of critical nodes and regulatory mechanisms for these pathways.
- Overview of inducers and inhibitors for non-apoptotic cell death.
Conclusions:
- Regulated necrotic cell death pathways present significant therapeutic potential.
- Targeting these pathways could lead to novel treatments for diseases.
- Further research is needed to fully unravel and exploit these cell death modalities.
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