{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:15:11Z","timestamp":1791969311462,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H03071"],"award-info":[{"award-number":["22H03071"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The deposition of \u03b1\u2010synuclein (\u03b1\u2010Syn) fibrils in neuronal cells has been implicated as a causative factor in Parkinson's disease (PD) and dementia with Lewy Bodies (DLB). \u03b1\u2010Syn can be degraded by autophagy, proteasome, and chaperone\u2010mediated autophagy, and previous studies have suggested the potency of certain cathepsins, lysosomal proteases, for \u03b1\u2010Syn degradation. However, no studies have comprehensively evaluated all cathepsins. Here, we evaluated the efficacy of all 15 cathepsins using a cell model of \u03b1\u2010Syn fibril propagation and found that overexpression of cathepsin L (CTSL) was the most effective in preventing the accumulation of \u03b1\u2010Syn aggregates. CTSL\u2010mediated degradation of \u03b1\u2010Syn aggregates was dependent on the autophagy machinery, and CTSL itself promoted autophagy flux. Interestingly, CTSL was effective in autophagic degradation of wild\u2010type (WT) \u03b1\u2010Syn, but not in the case of A53T and E46K missense mutations, which are causative for familial PD. These results suggest that CTSL is a potential therapeutic strategy for sporadic PD pathology in WT \u03b1\u2010Syn.<\/jats:p>","DOI":"10.1111\/gtc.13099","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T08:10:39Z","timestamp":1708157439000},"page":"328-336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cathepsin L prevents the accumulation of alpha\u2010synuclein fibrils in the cell"],"prefix":"10.1111","volume":"29","author":[{"given":"Ayumi","family":"Matsuki","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Basic Geriatrics Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-1319","authenticated-orcid":false,"given":"Atsushi","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoaki","family":"Matoba","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto 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