{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:37:17Z","timestamp":1790743037848,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,3,17]],"date-time":"2011-03-17T00:00:00Z","timestamp":1300320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","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":[[2011,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Prenatal exposure to mercury causes neurodevelopmental disorders and neurological pathologies in infants, such as microcephaly and mental retardation. Despite critical importance, the molecular interactions leading to mercury toxicity are yet to be elucidated. We first used a cell\u2010free assay to investigate mercury effects on purified \u03b3\u2010secretase activity. Next, we treated adult\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                      with mercury and collected control and mercury\u2010treated embryos, which were subjected to mild hypotonic protein extraction, or immunostained to reveal nervous system morphology. Embryos left to develop into adults were examined for wing phenotypes. Relative to control metals, we found that mercury strongly inhibits\n                      <jats:italic>in vitro<\/jats:italic>\n                      \u03b3\u2010secretase processing of both amyloid\u2010\u03b2 precursor protein (APP) and Notch. Mercury inhibited APP and Notch cleavage in a dose\u2010dependent manner, with IC\n                      <jats:sub>50<\/jats:sub>\n                      values of 50\u2010125 nM, and is therefore comparable in potency to benchmark \u03b3\u2010secretase inhibitors. Immunoblot analysis of embryonic protein extracts showed that mercury inhibits Notch cleavage by \u03b3\u2010secretase\n                      <jats:italic>in vivo.<\/jats:italic>\n                      This is accompanied by severe neurodevelopmental abnormalities in embryos and adult wing\u2010notching phenotypes. Our findings provide first evidence that mercury is a direct and potent \u03b3\u2010secretase inhibitor and suggest that inhibition of \u03b3\u2010secretase and disruption of the Notch developmental pathway potentially contribute to mercury\u2010induced toxicity in the nervous system.\u2014Alattia, J\u2010R., Kuraishi, T., Dimitrov, M., Chang, I., Lemaitre, B., Fraering, P. C. Mercury is a direct and potent \u03b3\u2010secretase inhibitor affecting Notch processing and development in\n                      <jats:italic>Drosophila<\/jats:italic>\n                      .\n                      <jats:italic>FASEB J.<\/jats:italic>\n                      25, 2287\u20102295 (2011).\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>\n                  <\/jats:sec>","DOI":"10.1096\/fj.10-174078","type":"journal-article","created":{"date-parts":[[2011,3,18]],"date-time":"2011-03-18T00:40:37Z","timestamp":1300408837000},"page":"2287-2295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Mercury is a direct and potent \u03b3\u2010secretase inhibitor affecting Notch processing and development in\n                    <i>Drosophila<\/i>"],"prefix":"10.1096","volume":"25","author":[{"given":"Jean\u2010Ren\u00e9","family":"Alattia","sequence":"first","affiliation":[{"name":"Brain Mind Institute Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Kuraishi","sequence":"additional","affiliation":[{"name":"Global Health Institute, School of Life Sciences, Swiss Federal Institute of Technology Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitko","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Brain Mind Institute Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Chang","sequence":"additional","affiliation":[{"name":"Brain Mind Institute Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Lemaitre","sequence":"additional","affiliation":[{"name":"Global Health Institute, School of Life Sciences, Swiss Federal Institute of Technology Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C.","family":"Fraering","sequence":"additional","affiliation":[{"name":"Brain Mind Institute Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2008.01.016"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2006.08.002"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339702500612"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2008.12.011"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858405278922"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1475"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.03.010"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.07.110191.002235"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05041.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501368200"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65010434.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/334071a0"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0269-7491(87)90173-4"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07055"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(95)02965-B"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200708127"},{"key":"e_1_2_5_18_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1073\/pnas.98.1.229","article-title":"Presenilin\u2010mediated trans\u2010membrane cleavage is required for Notch signal transduction in Drosophila","volume":"98","author":"Struhl G.","year":"2001","journal-title":"Proc. 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