Unveiling the Roles of Cysteine Proteinases F and W: From Structure to Pathological Implications and Therapeutic Targets

Author:

Zdravkova Kristina1ORCID,Mijanovic Olja2,Brankovic Ana3ORCID,Ilicheva Polina M.4ORCID,Jakovleva Aleksandra5ORCID,Karanovic Jelena6,Pualic Milena7,Pualic Dusan8,Rubel Aleksandr A.9ORCID,Savvateeva Lyudmila V.10,Parodi Alessandro11ORCID,Zamyatnin Andrey A.1213ORCID

Affiliation:

1. AD Alkaloid Skopje, Boulevard Alexander the Great 12, 1000 Skopje, North Macedonia

2. Dia-M, LCC, 7 b.3 Magadanskaya Str., 129345 Moscow, Russia

3. Department of Forensic Sciences, Faculty of Forensic Sciences and Engineering, University of Criminal Investigation and Police Studies, Cara Dusana 196, 11000 Belgrade, Serbia

4. Institute of Chemistry, Saratov State University, Astrakhanskaya Street 83, 410012 Saratov, Russia

5. HoxLife Science GmbH, Gutleutstraße 169-171, 60327 Frankfurt am Main, Germany

6. Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444A, 11000 Belgrade, Serbia

7. Institute Cardiovascular Diseases Dedinje, Heroja Milana Tepica 1, 11000 Belgrade, Serbia

8. Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia

9. Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia

10. Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia

11. Research Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia

12. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia

13. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

Abstract

Cysteine cathepsins F and W are members of the papain-like cysteine protease family, which have distinct structural features and functional roles in various physiological and pathological processes. This review provides a comprehensive overview of the current understanding of the structure, biological functions, and pathological implications of cathepsins F and W. Beginning with an introduction to these proteases, we delve into their structural characteristics and elucidate their unique features that dictate their enzymatic activities and substrate specificity. We also explore the intricate involvement of cathepsins F and W in malignancies, highlighting their role as potential biomarkers and therapeutic targets in cancer progression. Furthermore, we discuss the emerging roles of these enzymes in immune response modulation and neurological disorders, shedding light on their implications in autoimmune and neurodegenerative diseases. Finally, we review the landscape of inhibitors targeting these proteases, highlighting their therapeutic potential and challenges in clinical translation. This review brings together the diverse facets of cysteine cathepsins F and W, providing insights into their roles in health and disease and guiding future investigations for therapeutic advances.

Funder

Russian Science Foundation

Publisher

MDPI AG

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