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Cysteine cathepsins and their potential in clinical therapy and biomarker discovery
1Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Ljubljana, Slovenia; Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Ljubljana, Slovenia.
Abstract:
Since their discovery, cysteine cathepsins were generally considered to be involved mainly in the nonspecific bulk protein degradation that takes place within the lysosomes. However, it has become clear that their proteolytical activity can also influence various specific pathological processes such as cancer, arthritis, and atherosclerosis. Furthermore, their localization was found not to be limited strictly to the lysosomes. In the light of those findings, it is not surprising that cysteine cathepsins are currently considered as highly relevant clinical targets. Moreover, recent development of proteomic-based methods for identification of novel physiological substrates of proteases provides a major opportunity also in the field of cysteine cathepsins. In this review, we will therefore present cysteine cathepsin roles in disease progression and discuss their potential relevance as prognostic and diagnostic biomarkers.
Insights
Cysteine cathepsins, once thought only for protein breakdown, are now key targets in diseases like cancer. Their roles in specific pathologies and as biomarkers are increasingly recognized.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Cysteine cathepsins were traditionally viewed as lysosomal enzymes for bulk protein degradation.
- Emerging evidence highlights their involvement in specific pathological processes, including cancer, arthritis, and atherosclerosis.
- Their cellular localization extends beyond lysosomes, indicating broader functional roles.
Purpose of the Study:
- To review the multifaceted roles of cysteine cathepsins in disease progression.
- To discuss the potential of cysteine cathepsins as prognostic and diagnostic biomarkers.
- To explore the impact of novel proteomic methods in identifying cysteine cathepsin substrates.
Main Methods:
- Literature review of studies on cysteine cathepsins in disease.
- Analysis of proteomic data identifying protease substrates.
- Synthesis of current understanding of cysteine cathepsin functions.
Main Results:
- Cysteine cathepsins are implicated in the pathogenesis of major diseases.
- Their altered localization and activity contribute to disease states.
- Proteomic advancements are revealing new physiological substrates and functions.
Conclusions:
- Cysteine cathepsins represent significant clinical targets due to their roles in disease.
- Their potential as diagnostic and prognostic biomarkers warrants further investigation.
- Understanding their expanded functions is crucial for therapeutic development.
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