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Review
. 2020 May 12;21(1):111.
doi: 10.1186/s12931-020-01381-5.

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

Affiliations
Review

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

Ryan Brown et al. Respir Res. .

Abstract

Dysregulated expression and activity of cathepsin S (CTSS), a lysosomal protease and a member of the cysteine cathepsin protease family, is linked to the pathogenesis of multiple diseases, including a number of conditions affecting the lungs. Extracellular CTSS has potent elastase activity and by processing cytokines and host defense proteins, it also plays a role in the regulation of inflammation. CTSS has also been linked to G-coupled protein receptor activation and possesses an important intracellular role in major histocompatibility complex class II antigen presentation. Modulated CTSS activity is also associated with pulmonary disease comorbidities, such as cancer, cardiovascular disease, and diabetes. CTSS is expressed in a wide variety of immune cells and is biologically active at neutral pH. Herein, we review the significance of CTSS signaling in pulmonary diseases and associated comorbidities. We also discuss CTSS as a plausible therapeutic target and describe recent and current clinical trials examining CTSS inhibition as a means for treatment.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Mechanisms of CTSS regulation and function

References

    1. Lomas DA. Does protease-Antiprotease imbalance explain chronic obstructive pulmonary disease? Ann Am Thorac Soc. 2016;13(Suppl 2):S130–S137. - PubMed
    1. Patel S, Homaei A, El-Seedi HR, Akhtar N. Cathepsins: proteases that are vital for survival but can also be fatal. Biomed Pharmacother. 2018;105:526–532. doi: 10.1016/j.biopha.2018.05.148. - DOI - PMC - PubMed
    1. Garcia-Touchard A, Henry TD, Sangiorgi G, Spagnoli LG, Mauriello A, Conover C, Schwartz RS. Extracellular proteases in atherosclerosis and restenosis. Arterioscler Thromb Vasc Biol. 2005;25:1119–1127. doi: 10.1161/01.ATV.0000164311.48592.da. - DOI - PubMed
    1. Taggart C, Mall MA, Lalmanach G, Cataldo D, Ludwig A, Janciauskiene S, Heath N, Meiners S, Overall CM, Schultz C, et al. Protean proteases: at the cutting edge of lung diseases. Eur Respir J. 2017;49(2):1501200. - PubMed
    1. Leiberman J. Letter: familial variation of leukocyte lysosomal protease and serum alpha 1-antitrypsin as determinants in chronic obstructive pulmonary diseases. Am Rev Respir Dis. 1973;108:1019–1020. - PubMed

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