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The Role of Caspase Family in Acute Brain Injury: The Potential Therapeutic Targets in the Future
Anke Zhang1, Zeyu Zhang1, Yibo Liu1
1Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Abstract:
The caspase family is commonly involved in the pathophysiology of acute brain injury (ABI) through complex apoptotic, pyroptotic, and inflammatory pathways. Current translational strategies for caspase modulation in ABI primarily focus on caspase inhibitors. Because there are no caspase-inhibiting drugs approved for clinical use on the market, the development of caspase inhibitors remains an attractive challenge for researchers and clinicians. Therefore, we conducted the present review with the aim of providing a comprehensive introduction of caspases in ABI. In this review, we summarized the available evidence and potential mechanisms regarding the biological function of caspases. We also reviewed the therapeutic effects of caspase inhibitors on ABI and its subsequent complications. However, various important issues remain unclear, prompting further verification of the efficacy and safety regarding clinical application of caspase inhibitors. We believe that our work will be helpful to further understand the critical role of the caspase family and will provide novel therapeutic potential for ABI treatment.
Insights
This review explores caspases in acute brain injury (ABI), highlighting their role in cell death and inflammation. Caspase inhibitors show therapeutic potential for ABI, but further research is needed for clinical application.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Caspases are key enzymes in apoptosis, pyroptosis, and inflammation, significantly impacting acute brain injury (ABI) pathophysiology.
- Current therapeutic strategies for ABI predominantly target caspase modulation, primarily through caspase inhibitors.
- The lack of approved caspase-inhibiting drugs necessitates further research and development in this area.
Purpose of the Study:
- To provide a comprehensive overview of caspases within the context of acute brain injury.
- To summarize existing evidence on the biological functions and mechanisms of caspases in ABI.
- To review the therapeutic efficacy of caspase inhibitors for ABI and associated complications.
Main Methods:
- Systematic literature review of studies investigating caspases in acute brain injury.
- Analysis of evidence regarding the biological roles and mechanisms of caspases.
- Evaluation of preclinical and clinical data on caspase inhibitors for ABI treatment.
Main Results:
- Caspases play a multifaceted role in ABI pathogenesis via apoptotic, pyroptotic, and inflammatory pathways.
- Caspase inhibitors demonstrate promising therapeutic effects in preclinical models of ABI.
- Significant questions regarding the clinical efficacy and safety of caspase inhibitors for ABI persist.
Conclusions:
- Caspases are critical mediators in the complex biological processes underlying acute brain injury.
- Caspase inhibitors represent a potential therapeutic avenue for ABI, warranting continued investigation.
- Further research is essential to validate the safety and efficacy of caspase inhibitors for human clinical use in ABI.
