{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:13:57Z","timestamp":1767834837723,"version":"3.49.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T00:00:00Z","timestamp":1389744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Prion disorders are associated with the accumulation of a misfolded form (PrP\n            <jats:sup>Sc<\/jats:sup>\n            ) of the normal prion protein, PrP\n            <jats:sup>C<\/jats:sup>\n            . Here, we show that estrogen acts as a regulator of the processes of both prion infection and prion maintenance. Estrogen was found to be cell biased in its effect; it protected cells against prion infection in a prevention mode and enabled prion maintenance in a treatment mode. These processes were regulated by the estrogen receptor subtypes Er\u03b1 and Er\u03b2. By using specific receptor agonists, Er\u03b1 was found to be the main receptor active in slowing prion infection, whereas in chronically infected cells, although Er\u03b1 allowed partial maintenance of PrP\n            <jats:sup>Sc<\/jats:sup>\n            levels, Er\u03b2 was the main receptor involved in maintaining PrP\n            <jats:sup>Sc<\/jats:sup>\n            in a treatment paradigm. A cell-biased effect of estrogen has been reported for other neurodegenerative disorders, including Alzheimer's disease. Estrogen's effect is dependent on the cell's health status, which impacts the use of estrogen. This work also identified that by targeting the estrogen receptors with the selective estrogen receptor modulators tamoxifen (Tam) and 4-hydroxy-tamoxifen (OHT), PrP\n            <jats:sup>Sc<\/jats:sup>\n            could be cleared from prion-infected cell culture. Tam and OHT had half-maximal inhibitory concentrations for clearance of PrP\n            <jats:sup>Sc<\/jats:sup>\n            of 0.47 \u03bcM and 0.14 nM, respectively. This work identifies further factors involved in the prion disease process, and through antagonism of the estrogen system, we demonstrate that the estrogen system is a target for controlling PrP\n            <jats:sup>Sc<\/jats:sup>\n            levels.\n          <\/jats:p>","DOI":"10.1128\/jvi.02936-13","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T05:06:37Z","timestamp":1384405597000},"page":"1342-1353","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["A Cell-Biased Effect of Estrogen in Prion Infection"],"prefix":"10.1128","volume":"88","author":[{"given":"Brendan","family":"Molloy","sequence":"first","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilary E. M.","family":"McMahon","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.06.095"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00103-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0495"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2006"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.20049"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.226"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(03)00360-1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(01)00179-9"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608128103"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2011.02251.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1224"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/654818"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1991.61"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.1.159"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.8.1666"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.002071"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2007.02.003"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.17.2123"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.24.2947"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.07.003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104391108"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033493"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.01.172"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.1.320-325.2000"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02559-06"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2496"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh238"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_3_2_30_2","first-page":"317","article-title":"Tamoxifen and metabolites in MCF7 cells: correlation between binding to estrogen receptor and inhibition of cell growth","volume":"42","author":"Coezy E","year":"1982","unstructured":"CoezyEBorgnaJRochefortH. 1982. Tamoxifen and metabolites in MCF7 cells: correlation between binding to estrogen receptor and inhibition of cell growth. Cancer Res. 42:317\u2013323.","journal-title":"Cancer Res."},{"key":"e_1_3_2_31_2","first-page":"112","article-title":"Bioactivities, estrogen receptor interactions, and plasminogen activator-inducing activities of tamoxifen and hydroxy-tamoxifen isomers in MCF-7 human breast cancer cells","volume":"44","author":"Katzenellenbogen B","year":"1984","unstructured":"KatzenellenbogenBNormanMEckertRPeltzSMangelW. 1984. Bioactivities, estrogen receptor interactions, and plasminogen activator-inducing activities of tamoxifen and hydroxy-tamoxifen isomers in MCF-7 human breast cancer cells. Cancer Res. 44:112\u2013119.","journal-title":"Cancer Res."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708372104"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.05.013"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm010254a"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0341"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm000170m"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0140"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.19726-0"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005153"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(02)00108-0"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2003.09.003"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1478-1336-2-3"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(200004)43:1<64::AID-NEU6>3.0.CO;2-7"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.8.1007"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2011.588725"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00025-3"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.041617498"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2005.01.009"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.3.584"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.139.11.4513"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.1242"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19971201)388:4<507::AID-CNE1>3.0.CO;2-6"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-221069"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.11162"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221451898"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.06.073"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.09.069"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1859"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.05.045"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3574-09.2009"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.17.1934"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.9.688"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.24.2959"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.2.295"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201544"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02936-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02936-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:47:30Z","timestamp":1646495250000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02936-13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,15]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,1,15]]}},"alternative-id":["10.1128\/JVI.02936-13"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02936-13","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,15]]},"assertion":[{"value":"2013-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}