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Published on: May 9, 2025
Therapeutic potential of targeting cathepsin S in pulmonary fibrosis
YoungJo Yoo1, Eun Choi1, Yejin Kim1
1Graduate School of Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul 120-720, Republic of Korea.
Abstract:
Cathepsin S (CTSS), a lysosomal protease, belongs to a family of cysteine cathepsin proteases that promote degradation of damaged proteins in the endolysosomal pathway. Aberrant CTSS expression and regulation are associated with the pathogenesis of several diseases, including lung diseases. CTSS overexpression causes a variety of pathological processes, including pulmonary fibrosis, with increased CTSS secretion and accelerated extracellular matrix remodeling. Compared to many other cysteine cathepsin family members, CTSS has unique features that it presents limited tissue expression and retains its enzymatic activity at a neutral pH, suggesting its decisive involvement in disease microenvironments. In this review, we investigated the role of CTSS in lung disease, exploring recent studies that have indicated that CTSS mediates fibrosis in unique ways, along with its structure, substrates, and distinct regulation. We also outlined examples of CTSS inhibitors in clinical and preclinical development and proposed CTSS as a potential therapeutic target for pulmonary fibrosis.
Insights
Cathepsin S (CTSS) is implicated in lung disease pathogenesis, particularly pulmonary fibrosis. Targeting CTSS offers a promising therapeutic strategy for treating lung conditions.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Cathepsin S (CTSS) is a lysosomal protease involved in protein degradation.
- Aberrant CTSS expression is linked to lung disease pathogenesis, including pulmonary fibrosis.
- CTSS exhibits unique characteristics like limited tissue expression and neutral pH activity.
Purpose of the Study:
- To review the role of CTSS in lung disease.
- To explore CTSS's unique mechanisms in mediating fibrosis.
- To discuss CTSS inhibitors and therapeutic potential for pulmonary fibrosis.
Main Methods:
- Literature review of recent studies on CTSS in lung disease.
- Analysis of CTSS structure, substrates, and regulation.
- Examination of CTSS inhibitors in clinical and preclinical development.
Main Results:
- CTSS overexpression drives pathological processes in pulmonary fibrosis.
- CTSS accelerates extracellular matrix remodeling.
- CTSS plays a decisive role in disease microenvironments.
Conclusions:
- CTSS is a significant factor in the pathogenesis of lung diseases, especially fibrosis.
- Understanding CTSS's unique features is crucial for therapeutic development.
- CTSS represents a potential therapeutic target for pulmonary fibrosis.
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