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Caspases--their role in apoptosis and other physiological processes as revealed by knock-out studies
Kenneth Sadowski-Debbing1, Johannes F Coy, Walter Mier
1Clinic for Craniomaxillofacial Surgery, Ahaus, Germany.
Abstract:
Caspases are crucial mediators of apoptosis, a form of physiological cell death. Their activation is carefully controlled by a philogenetically conserved death program, which is indispensable for the homeostasis and development of higher organisms. Dysregulation of apoptosis contributes to the pathogenesis of many human diseases. As effectors of the apoptotic machinery, caspases are considered potential therapeutic targets. In vitro studies have demonstrated the requirement of caspase activity for both the triggering phase as well as the execution of apoptosis, thus providing a molecular base for the fine-tuning of this process by pharmacological agents. The precise roles of the individual caspases in vivo and their functional relation to each other have been best demonstrated in genetically modified animals. The generation of single caspase-deficient mice have confirmed most of the data obtained in vitro and exposed some new aspects previously undetected in the cell culture system. Interestingly, inactivation of many caspases revealed not only their expected participation in apoptotic events as well as in the maturation of cytokines, but also provided hints about the role of at least some caspases in cell differentiation and stimulatory responses. In this review we will discuss what these studies have unveiled about the role of individual caspases in development, apoptosis, and inflammation, with particular focus on their role beyond the apoptotic process.
Insights
Caspases are key to apoptosis (programmed cell death) and maintaining health. Studies in genetically modified animals reveal caspases have roles beyond apoptosis, impacting development and inflammation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Caspases are essential enzymes regulating apoptosis, a vital process for organismal homeostasis and development.
- Dysregulation of apoptosis is implicated in various human diseases, making caspases potential therapeutic targets.
- In vitro studies established caspase activity's role in apoptosis initiation and execution.
Purpose of the Study:
- To review the roles of individual caspases in vivo, particularly beyond their known apoptotic functions.
- To discuss findings from genetically modified animal studies on caspase functions.
- To highlight the involvement of caspases in development, apoptosis, and inflammation.
Main Methods:
- Review of studies involving genetically modified animals, specifically caspase-deficient mice.
- Analysis of in vitro experimental data on caspase activity.
- Synthesis of current research on caspase functions in biological processes.
Main Results:
- In vivo studies largely confirmed in vitro findings regarding caspases' role in apoptosis and cytokine maturation.
- Genetically modified animals revealed novel caspase functions not observed in cell culture.
- Evidence suggests some caspases are involved in cell differentiation and immune responses.
Conclusions:
- Caspases play multifaceted roles in vivo, extending beyond apoptosis.
- Understanding these diverse functions is crucial for comprehending development, inflammation, and disease.
- Further research into non-apoptotic caspase roles may uncover new therapeutic strategies.