{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:21:52Z","timestamp":1791685312086,"version":"4.3.4"},"reference-count":152,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-926"],"award-info":[{"award-number":["075-15-2020-926"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Lysosomal proteases play a crucial role in maintaining cell homeostasis. Human cathepsin D manages protein turnover degrading misfolded and aggregated proteins and favors apoptosis in the case of proteostasis disruption. However, when cathepsin D regulation is affected, it can contribute to numerous disorders. The down-regulation of human cathepsin D is associated with neurodegenerative disorders, such as neuronal ceroid lipofuscinosis. On the other hand, its excessive levels outside lysosomes and the cell membrane lead to tumor growth, migration, invasion and angiogenesis. Therefore, targeting cathepsin D could provide significant diagnostic benefits and new avenues of therapy. Herein, we provide a brief overview of cathepsin D structure, regulation, function, and its role in the progression of many diseases and the therapeutic potentialities of natural and synthetic inhibitors and activators of this protease.<\/jats:p>","DOI":"10.3390\/pharmaceutics13060837","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T01:56:40Z","timestamp":1623031000000},"page":"837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Cathepsin D\u2014Managing the Delicate Balance"],"prefix":"10.3390","volume":"13","author":[{"given":"Olja","family":"Mijanovic","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia I.","family":"Petushkova","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Laboratory of Nanomedicine, Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Ave, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Brankovic","sequence":"additional","affiliation":[{"name":"Department of Forensic Engineering, University of Criminal Investigation and Police Studies, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9007-5764","authenticated-orcid":false,"given":"Boris","family":"Turk","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna B.","family":"Solovieva","sequence":"additional","affiliation":[{"name":"Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina I.","family":"Nikitkina","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Bolevich","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Sechenov University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7773-2435","authenticated-orcid":false,"given":"Peter S.","family":"Timashev","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Faculty of Chemistry, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"World-Class Research Center \u201cDigital Biodesign and Personalized Healthcare\u201d, Sechenov University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Parodi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Laboratory of Nanomedicine, Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Ave, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3046-4565","authenticated-orcid":false,"suffix":"Jr.","given":"Andrey A.","family":"Zamyatnin","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Laboratory of Nanomedicine, Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Ave, 354340 Sochi, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s10495-009-0452-5","article-title":"Regulation of apoptosis-associated lysosomal membrane permeabilization","volume":"15","author":"Johansson","year":"2010","journal-title":"Apoptosis"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Trivedi, P.C., Bartlett, J.J., and Pulinilkunnil, T. 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