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Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics
Published on: January 11, 2019
The therapeutic potential of targeting regulated non-apoptotic cell death
Kamyar Hadian1, Brent R Stockwell2
1Research Unit Signaling and Translation, Helmholtz Zentrum München, Neuherberg, Germany. kamyar.hadian@helmholtz-munich.de.
Abstract:
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.
Insights
Regulated cell death, beyond apoptosis, includes pathways like necroptosis and ferroptosis, offering new therapeutic targets for diseases. Understanding these non-apoptotic cell death mechanisms is key for future drug discovery.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Cell death is essential for organism development and homeostasis.
- Dysregulated cell death contributes to various diseases, including cancer and inflammatory conditions.
- Historically, apoptosis was the primary focus, but regulated necrosis pathways are now recognized.
Purpose of the Study:
- To review the regulatory pathways of various non-apoptotic cell death forms.
- To discuss small-molecule inhibitors for these pathways.
- To explore future prospects in drug discovery for controlling cell death.
Main Methods:
- Literature review of regulated cell death pathways.
- Analysis of molecular mechanisms governing necroptosis, pyroptosis, parthanatos, ferroptosis, cuproptosis, lysozincrosis, and disulfidptosis.
- Examination of existing and potential small-molecule inhibitors.
Main Results:
- Detailed description of multiple regulated non-apoptotic cell death pathways.
- Identification of key molecular players and signaling cascades.
- Overview of therapeutic strategies targeting these pathways.
Conclusions:
- Regulated non-apoptotic cell death pathways represent a complex and crucial area of biological research.
- Targeting these pathways offers promising therapeutic avenues for a range of diseases.
- Further drug discovery efforts are needed to harness the potential of controlling cell death.
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