{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:53:10Z","timestamp":1782276790659,"version":"3.54.5"},"reference-count":65,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T00:00:00Z","timestamp":1369699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG\u201020206"],"award-info":[{"award-number":["AG\u201020206"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:p>\n                    Aggregation and accumulation of A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    play an initiating role in Alzheimer's disease (AD); thus, selective lowering of A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    by \u03b3\u2010secretase modulators (GSMs) remains a promising approach to AD therapy. Based on evidence suggesting that steroids may influence A\u03b2 production, we screened 170 steroids at 10 \u03bcM for effects on A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    secreted from human APP\u2010overexpressing Chinese hamster ovary cells. Many acidic steroids lowered A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    , whereas many nonacidic steroids actually raised A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    . Studies on the more potent compounds showed that A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \u2010lowering steroids were bonafide GSMs and A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \u2010raising steroids were inverse GSMs. The most potent steroid GSM identified was 5\u03b2\u2010cholanic acid (EC\n                    <jats:sub>50<\/jats:sub>\n                    =5.7 \u03bcM; its endogenous analog lithocholic acid was virtually equipotent), and the most potent inverse GSM identified was 4\u2010androsten\u20103\u2010one\u201017\u03b2\u2010carboxylic acid ethyl ester (EC\n                    <jats:sub>50<\/jats:sub>\n                    =6.25 \u03bcM). In addition, we found that both estrogen and progesterone are weak inverse GSMs with further complex effects on APP processing. These data suggest that certain endogenous steroids may have the potential to act as GSMs and add to the evidence that cholesterol, cholesterol metabolites, and other steroids may play a role in modulating A\u03b2 production and thus risk for AD. They also indicate that acidic steroids might serve as potential therapeutic leads for drug optimization\/development.\u2014Jung, J. I., Ladd, T. B., Kukar, T., Price, A. R., Moore, B. D., Koo, E. H., Golde, T. E., Felsenstein, K. M., Steroids as \u03b3\u2010secretase modulators. FASEB J. 27, 3775\u20133785 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-225649","type":"journal-article","created":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T03:03:24Z","timestamp":1369796604000},"page":"3775-3785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Steroids as \u03b3\u2010secretase modulators"],"prefix":"10.1096","volume":"27","author":[{"given":"Joo In","family":"Jung","sequence":"first","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease College of Medicine University of Florida Gainesville Florida USA"},{"name":"Department of Neuroscience College of Medicine University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Ladd","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease College of Medicine University of Florida Gainesville Florida USA"},{"name":"Department of Neuroscience College of Medicine University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kukar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neurology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashleigh R.","family":"Price","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease College of Medicine University of Florida Gainesville Florida USA"},{"name":"Department of Neuroscience College of Medicine University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda D.","family":"Moore","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease College of Medicine University of Florida Gainesville Florida USA"},{"name":"Department of Neuroscience College of Medicine University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd E.","family":"Golde","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease College of Medicine University of Florida Gainesville Florida USA"},{"name":"Department of Neuroscience College of Medicine University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Felsenstein","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease College of Medicine University of Florida Gainesville Florida USA"},{"name":"Department of Neuroscience College of Medicine University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(00)00043-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0196-93"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00564-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt121"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.50.31894"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/359325a0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8191290"},{"key":"e_1_2_7_9_1","first-page":"289","article-title":"The role of A\u03b242 in Alzheimer's disease","volume":"92","author":"Steven G Y.","journal-title":"J. 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