{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:06:44Z","timestamp":1791328004306,"version":"4.3.1"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,4,23]]},"abstract":"<jats:p>Prion diseases such as Creutzfeldt\u2013Jakob disease (CJD) are incurable and rapidly fatal neurodegenerative diseases. Because prion protein (PrP) is necessary for prion replication but dispensable for the host, we developed the PrP\u2013FRET-enabled high throughput assay (PrP\u2013FEHTA) to screen for compounds that decrease PrP expression. We screened a collection of drugs approved for human use and identified astemizole and tacrolimus, which reduced cell-surface PrP and inhibited prion replication in neuroblastoma cells. Tacrolimus reduced total cellular PrP levels by a nontranscriptional mechanism. Astemizole stimulated autophagy, a hitherto unreported mode of action for this pharmacophore. Astemizole, but not tacrolimus, prolonged the survival time of prion-infected mice. Astemizole is used in humans to treat seasonal allergic rhinitis in a chronic setting. Given the absence of any treatment option for CJD patients and the favorable drug characteristics of astemizole, including its ability to cross the blood\u2013brain barrier, it may be considered as therapy for CJD patients and for prophylactic use in familial prion diseases. Importantly, our results validate PrP-FEHTA as a method to identify antiprion compounds and, more generally, FEHTA as a unique drug discovery platform.<\/jats:p>","DOI":"10.1073\/pnas.1303510110","type":"journal-article","created":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T21:35:20Z","timestamp":1364852120000},"page":"7044-7049","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":94,"title":["Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents"],"prefix":"10.1073","volume":"110","author":[{"given":"Yervand Eduard","family":"Karapetyan","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Franco","family":"Sferrazza","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Ottenberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Spicer","sequence":"additional","affiliation":[{"name":"Lead Identification, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Chase","sequence":"additional","affiliation":[{"name":"Lead Identification, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Fallahi","sequence":"additional","affiliation":[{"name":"Information Technology and Informatics, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hodder","sequence":"additional","affiliation":[{"name":"Lead Identification, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Weissmann","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne Ida","family":"Lasm\u00e9zas","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6801762"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)91412-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/381743a0"},{"key":"e_1_3_3_4_2","unstructured":"World Health Organization (2012) Variant Creutzfeldt-Jakob disease. 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