{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:15:20Z","timestamp":1788293720826,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["HI16C0965"],"award-info":[{"award-number":["HI16C0965"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The conversion of cellular prion protein (PrPC) into pathogenic prion isoforms (PrPSc) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrPSc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg\/kg) exhibited prolonged survival times (159 \u00b1 28.6 days) compared to nontreated hamsters (135 \u00b1 9.9 days) as well as reduced PrPSc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg\/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg\/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood\u2013brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.<\/jats:p>","DOI":"10.3390\/ijms241512241","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T09:22:38Z","timestamp":1690795358000},"page":"12241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Yeong-Gon","family":"Choi","sequence":"first","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Youngdeungpo-gu, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byungki","family":"Jang","sequence":"additional","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Youngdeungpo-gu, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Youngdeungpo-gu, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Woo","family":"Choi","sequence":"additional","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Youngdeungpo-gu, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong Yeal","family":"Lee","sequence":"additional","affiliation":[{"name":"Il Yang Pharm Co., Ltd., 37, Hagal-ro, 136beon-gil, Giheung-gu, Yongin-si 17096, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Jin","family":"Cho","sequence":"additional","affiliation":[{"name":"Il Yang Pharm Co., Ltd., 37, Hagal-ro, 136beon-gil, Giheung-gu, Yongin-si 17096, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Youp","family":"Kim","sequence":"additional","affiliation":[{"name":"Il Yang Pharm Co., Ltd., 37, Hagal-ro, 136beon-gil, Giheung-gu, Yongin-si 17096, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Kyoung","family":"Lim","sequence":"additional","affiliation":[{"name":"Il Yang Pharm Co., Ltd., 37, Hagal-ro, 136beon-gil, Giheung-gu, Yongin-si 17096, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Il Yang Pharm Co., Ltd., 37, Hagal-ro, 136beon-gil, Giheung-gu, Yongin-si 17096, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9251-8442","authenticated-orcid":false,"given":"Eun-Kyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Youngdeungpo-gu, Seoul 07247, Republic of Korea"},{"name":"Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Youngdeungpo-gu, Seoul 07247, Republic of Korea"},{"name":"Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1146\/annurev.pathmechdis.3.121806.154326","article-title":"Molecular mechanisms of prion pathogenesis","volume":"3","author":"Aguzzi","year":"2008","journal-title":"Annu. 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