{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:43:53Z","timestamp":1773009833151,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2021R1A2C1013213"],"award-info":[{"award-number":["2021R1A2C1013213"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2022R1C1C2004792"],"award-info":[{"award-number":["2022R1C1C2004792"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2017R1A6A1A03015876"],"award-info":[{"award-number":["2017R1A6A1A03015876"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2021R1A6A3A01086488"],"award-info":[{"award-number":["2021R1A6A3A01086488"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2021R1A6C101C369"],"award-info":[{"award-number":["2021R1A6C101C369"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transboundary and Emerging Diseases"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Prion diseases are fatal, irreversible, and infectious neurodegenerative diseases caused by proteinase K\u2010resistant prion protein (PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    ). Against PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , several endogenous proteases involved in cellular degradation mechanisms can be activated to remove PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    . However, since PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    shows proteinase K resistance, we presumed that undegradable PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    induces positive feedback on the overactivation of the cellular degradation mechanisms and is correlated with proteolytic stress and exacerbation of the progression of prion diseases. We investigated the expression pattern of proteolytic stress\u2010related proteins in the brains of ME7 scrapie\u2010infected mice at 7 months postinfection and sporadic Creutzfeldt\u2013Jakob disease (CJD) patients using western blotting and immunohistochemistry (IHC). In addition, we analyzed the 3D structure and binding complexes of prion protein (PrP) with nattokinase and lumbrokinase using in silico programs, including SWISS\u2010MODEL and HawkDock. To fundamentally reduce proteolytic stress by the degradation of PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , we performed an in vitro evaluation of the PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    degradation abilities of fibrinolytic enzymes, including nattokinase and lumbrokinase. Furthermore, we assessed the protective effects of nattokinase and lumbrokinase in ME7 scrapie\u2010infected mice. We observed an abnormal accumulation of proteolytic stress\u2010related proteins, including CD10, cathepsin B, cathepsin D, and matrix metalloproteinase 9 (MMP9), in the brains of ME7 scrapie\u2010infected mice and sporadic CJD patients. In addition, we identified that nattokinase and lumbrokinase can stably bind to PrP. Furthermore, we identified significant in vitro degradation of PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    derived from ME7 scrapie\u2010infected mice and sporadic CJD patients by nattokinase and lumbrokinase. Last, we found in vivo protective effects of nattokinase and lumbrokinase against prion disease in ME7 scrapie\u2010infected mice. To the best of our knowledge, this is the first report on the identification of proteolytic stress\u2010related novel potential biomarkers and the therapeutic potential of nattokinase and lumbrokinase for prion diseases.\n                  <\/jats:p>","DOI":"10.1155\/tbed\/9527934","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T22:34:25Z","timestamp":1741041265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Abnormal Expression of Proteolytic Stress\u2010Related Proteins and Protective Effect of Fibrinolytic Enzymes in Prion Diseases"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-5457","authenticated-orcid":false,"given":"Yong-Chan","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-4370","authenticated-orcid":false,"given":"Sae-Young","family":"Won","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-9994","authenticated-orcid":false,"given":"Byung-Hoon","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1675487"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00747-z"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0011-4"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/352340a0"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02153-7"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336896.2015.1118603"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024364"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.14053"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.14309"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30615-2"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336896.2019.1689789"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-4272-5"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00975"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201612165"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006379"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70020721.x"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.4161\/pri.22850"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062817"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03174-6"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309147"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-0403-y"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf803072r"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.2174\/1871527318666191021150002"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz397"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/1177271918785130"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/783971"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2010.14.2.71"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep11601"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/35044100"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.01.017"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10.163600"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)05110-2"}],"container-title":["Transboundary and Emerging Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/tbed\/9527934","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/tbed\/9527934","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/tbed\/9527934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:59:54Z","timestamp":1773003594000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/tbed\/9527934"}},"subtitle":[],"editor":[{"given":"Nan-hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1155\/tbed\/9527934"],"URL":"https:\/\/doi.org\/10.1155\/tbed\/9527934","archive":["Portico"],"relation":{},"ISSN":["1865-1674","1865-1682"],"issn-type":[{"value":"1865-1674","type":"print"},{"value":"1865-1682","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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