{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:45:16Z","timestamp":1791409516417,"version":"4.3.3"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T00:00:00Z","timestamp":1347408000000},"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\u201009464"],"award-info":[{"award-number":["AG\u201009464"]}],"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":[[2012,12]]},"abstract":"<jats:p>\n                    The pathways leading specifically to the toxic A\u03b242 peptide production, a key event in Alzheimer's disease (AD), are unknown. While searching for pathways that mediate pathological increases of A\u03b242, we identified Aftin\u20104, a new compound that selectively and potently increases A\u03b242 compared to DMSO (N2a cells: 7\u2010fold; primary neurons: 4\u2010fold; brain lysates: 2\u2010fold) with an EC\n                    <jats:sub>50<\/jats:sub>\n                    of 30 \u03bcM. These results were confirmed by ELISA and IP\u2010WB. Using affinity chromatography and mass spectrometry, we identified 3 proteins (VDAC1, prohibitin, and mitofilin) relevant to AD that interact with Aftin\u20104, but not with a structurally similar but inactive molecule. Electron microscopy studies demonstrated that Aftin\u20104 induces a reversible mitochondrial phenotype reminiscent of the one observed in AD brains. Sucrose gradient fractionation showed that Aftin\u20104 perturbs the subcellular localization of \u03b3\u2010secretase components and could, therefore, modify \u03b3\u2010secretase specificity by locally altering its membrane environment. Remarkably, Aftin\u20104 shares all these properties with two other \u201cAD accelerator\u201d compounds. In summary, treatment with three A\u03b242 raising agents induced similar biochemical alterations that lead to comparable cellular phenotypes\n                    <jats:italic>in vitro<\/jats:italic>\n                    , suggesting a common mechanism of action involving three structural cellular targets.\u2014Bettayeb, K., Oumata, N., Zhang, Y., Luo, W., Bustos, V., Galons, H., Greengard, P., Meijer, L., Flajolet, M. Small\u2010molecule inducers of A\u03b2\u201042 peptide production share a common mechanism of action.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 5115\u20135123 (2012).\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.12-212985","type":"journal-article","created":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T21:41:29Z","timestamp":1347486089000},"page":"5115-5123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Small\u2010molecule inducers of A\u03b2\u201042 peptide production share a common mechanism of action"],"prefix":"10.1096","volume":"26","author":[{"given":"Karima","family":"Bettayeb","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience The Rockefeller University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nassima","family":"Oumata","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacochimie, Unit\u00e9 Mixte de Recherche (UMR) Centre National de la Recherche Scientifique (CNRS) Universit\u00e9 Paris\u2010Descartes Paris France"},{"name":"ManRos Therapeutics Centre de Perharidy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience The Rockefeller University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Luo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience The Rockefeller University New York New York 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