{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:24:00Z","timestamp":1791685440573,"version":"4.3.4"},"reference-count":91,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":33,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-173385"],"award-info":[{"award-number":["PJT-173385"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021730","name":"Alberta Prion Research Institute","doi-asserted-by":"crossref","award":["201600035"],"award-info":[{"award-number":["201600035"]}],"id":[{"id":"10.13039\/501100021730","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,22]]},"abstract":"<jats:p>\n                    Prion diseases are fatal, infectious, and incurable neurodegenerative conditions affecting humans and animals, caused by the misfolding of the cellular prion protein (PrP\n                    <jats:sup>C<\/jats:sup>\n                    ) into its pathogenic isoform, PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    . In humans, sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent prion disease. Recently, we demonstrated that treatment with the FDA-approved anti-HIV drug efavirenz (EFV) significantly reduced PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    and extended survival of scrapie prion\u2013infected mice. Among other effects, EFV activates the brain-specific cholesterol-metabolizing enzyme, CYP46A1, which converts cholesterol into 24S-hydroxycholesterol (24S-HC). However, drugs effective against scrapie prions often fail in human prion diseases, and a relation of the antiprion effects of EFV to CYP46A1 activation is not established. Thus, we evaluated EFV treatment in mice overexpressing human PrP\n                    <jats:sup>C<\/jats:sup>\n                    infected with human sCJD prions. Oral, low-dose EFV treatment starting at 30 or 130 days postinfection significantly slowed disease progression and extended their survival. At early clinical stage, we observed reduced PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    accumulation, decreased cholesterol and lipid droplet content, and elevated CYP46A1 and 24S-HC levels in EFV-treated mice. Overexpression of CYP46A1 in prion-infected neuronal cells reduced PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    levels and increased 24S-HC, indicating that antiprion effects of EFV correlate with CYP46A1 activation. These findings highlight EFV as a safe and efficacious therapeutic candidate for human prion diseases.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.190296","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T12:23:26Z","timestamp":1750422206000},"source":"Crossref","is-referenced-by-count":7,"title":["Treatment with efavirenz extends survival in a Creutzfeldt-Jakob disease model by regulating brain cholesterol metabolism"],"prefix":"10.1172","volume":"10","author":[{"given":"Tahir","family":"Ali","sequence":"first","affiliation":[{"name":"Calgary Prion Research Unit, Faculty of Veterinary Medicine;"},{"name":"Hotchkiss Brain Institute, Cumming School of Medicine; and"},{"name":"Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Cashion","sequence":"additional","affiliation":[{"name":"Calgary Prion Research Unit, 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