{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:11:24Z","timestamp":1791349884732,"version":"4.3.1"},"reference-count":55,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Prion diseases are fatal neurodegenerative disorders involving the abnormal folding of a native cellular protein, named PrPC, to a malconformed aggregation-prone state, enriched in beta sheet secondary structure, denoted PrPSc. Recently, autophagy has garnered considerable attention as a cellular process with the potential to counteract neurodegenerative diseases of protein aggregation such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. Stimulation of autophagy by chemical compounds has also been shown to reduce PrPSc in infected neuronal cells and prolong survival times in mice models. Consistent with previous reports we demonstrate that autophagic flux is increased in chronically infected cells. However, in contrast to recent findings we show that autophagy is not causative of a reduction in scrapie burden. We report that in infected neuronal cells different compounds known to stimulate autophagy are ineffective in increasing autophagic flux and in reducing PrPSc. We further demonstrate that tamoxifen and its metabolite 4-hydroxytamoxifen lead to prion degradation in an autophagy-independent manner by diverting the trafficking of both PrP and cholesterol to lysosomes. Because tamoxifen represents a well-characterized, widely available pharmaceutical our data indicate that it may have applications in the therapy of prion diseases.<\/jats:p>","DOI":"10.1242\/jcs.114801","type":"journal-article","created":{"date-parts":[[2013,2,16]],"date-time":"2013-02-16T04:02:49Z","timestamp":1360987369000},"source":"Crossref","is-referenced-by-count":28,"title":["4-hydroxytamoxifen leads to PrPSc clearance by conveying both PrPC and PrPSc to lysosomes independently of autophagy"],"prefix":"10.1242","author":[{"given":"Ludovica","family":"Marzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zrinka","family":"Marijanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Browman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeina","family":"Chamoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Caputo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zurzolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2021042613241684200_b1","doi-asserted-by":"publisher","first-page":"361","DOI":"10.4161\/auto.5.3.7662","article-title":"Autophagy induction by trehalose counteracts cellular prion infection.","volume":"5","author":"Aguib","year":"2009","journal-title":"Autophagy"},{"key":"2021042613241684200_b2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy.","volume":"224","author":"Bolte","year":"2006","journal-title":"J. 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