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Updated: Sep 21, 2026
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Apoptosis and age-related disorders: role of caspase-dependent and caspase-independent pathways
1Chair of Molecular Toxicology, Faculty of Biology, University of Konstanz, P.O. Box X911, Germany. pn10@le.ac.uk
Abstract:
The execution of the apoptotic program involves a relatively limited number of pathways that converge on the activation of the caspase family of proteases. However, there is increasing evidence that other protease families may contribute to produce apoptotic-like features. This has posed the question as to whether caspase inhibitors may then be used to treat diseases characterised by an excess apoptosis. In several neurodegenerative diseases including acute neuronal loss as in stroke or slowly developing diseases at least two major events contribute to neurodegeneration: the loss of neuronal connectivity and cell loss. In many of these conditions, mitochondrial dysfunction and the resulting ATP depletion may preclude caspase activation, and consequently switch execution of cell death towards necrosis. A block or partial inhibition of the typical apoptotic demise may have profound implications in vivo, as persistence within the nervous system of damaged, but 'undead' cells, followed by delayed lysis may favour neuroinflammatory reactions. Furthermore, caspases may be involved in loss of neurons, but not in the loss of connectivity that seems to initiate degenerative processes in the nervous system. Some recent findings, which suggest that degenerating neurons may use multiple execution pathways will be discussed.
Insights
Apoptosis involves caspases, but other proteases may cause cell death. Caspase inhibitors might treat diseases with excess apoptosis, but alternative cell death pathways exist in neurodegeneration.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Apoptosis is a programmed cell death pathway primarily mediated by caspases.
- Neurodegenerative diseases involve neuronal loss and connectivity deficits, often linked to mitochondrial dysfunction.
- Mitochondrial dysfunction can inhibit caspase activation, potentially leading to necrosis instead of apoptosis.
Purpose of the Study:
- To investigate the role of proteases beyond caspases in apoptosis-like cell death.
- To explore the therapeutic potential of caspase inhibitors in diseases with excessive apoptosis.
- To understand the implications of alternative cell death execution pathways in neurodegeneration.
Main Methods:
- Review of existing literature on apoptotic pathways and protease families.
- Analysis of mechanisms underlying cell death in neurodegenerative conditions.
- Discussion of recent findings on multiple execution pathways in degenerating neurons.
Main Results:
- Evidence suggests non-caspase proteases can contribute to apoptotic-like features.
- In neurodegeneration, ATP depletion may shift cell death from apoptosis to necrosis.
- Inhibition of apoptosis can lead to 'undead' cells, promoting neuroinflammation.
Conclusions:
- Caspase-independent pathways play a role in cell death, complicating caspase inhibitor therapy.
- Understanding diverse cell death mechanisms is crucial for treating neurodegenerative diseases.
- Neurons may utilize multiple execution pathways during degeneration, necessitating a broader therapeutic approach.
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