{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:08:16Z","timestamp":1787004496025,"version":"build-2736575974"},"reference-count":46,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:p>The essential metals iron, zinc and copper deposit near the A\u03b2 (amyloid \u03b2-peptide) plaques in the brain cortex of AD (Alzheimer's disease) patients. Plaque-associated iron and zinc are in neurotoxic excess at 1\u00a0mM concentrations. APP (amyloid precursor protein) is a single transmembrane metalloprotein cleaved to generate the 40\u201342-amino-acid A\u03b2s, which exhibit metal-catalysed neurotoxicity. In health, ubiquitous APP is cleaved in a non-amyloidogenic pathway within its A\u03b2 domain to release the neuroprotective APP ectodomain, APP(s). To adapt and counteract metal-catalysed oxidative stress, as during reperfusion from stroke, iron and cytokines induce the translation of both APP and ferritin (an iron storage protein) by similar mechanisms. We reported that APP was regulated at the translational level by active IL (interleukin)-1 (IL-1-responsive acute box) and IRE (iron-responsive element) RNA stem\u2013loops in the 5\u2032 untranslated region of APP mRNA. The APP IRE is homologous with the canonical IRE RNA stem\u2013loop that binds the iron regulatory proteins (IRP1 and IRP2) to control intracellular iron homoeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability. The APP IRE interacts with IRP1 (cytoplasmic cis-aconitase), whereas the canonical H-ferritin IRE RNA stem\u2013loop binds to IRP2 in neural cell lines, and in human brain cortex tissue and in human blood lysates. The same constellation of RNA-binding proteins [IRP1\/IRP2\/poly(C) binding protein] control ferritin and APP translation with implications for the biology of metals in AD.<\/jats:p>","DOI":"10.1042\/bst0361282","type":"journal-article","created":{"date-parts":[[2008,12,2]],"date-time":"2008-12-02T12:27:13Z","timestamp":1228220833000},"page":"1282-1287","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer's disease"],"prefix":"10.1042","volume":"36","author":[{"given":"Jack\u00a0T.","family":"Rogers","sequence":"first","affiliation":[{"name":"Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley\u00a0I.","family":"Bush","sequence":"additional","affiliation":[{"name":"Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyan-Hee","family":"Cho","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah\u00a0H.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew\u00a0M.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi\u00a0L.","family":"Friedlich","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debomoy\u00a0K.","family":"Lahiri","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and of Medical and Molecular Genetics, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u00a0J.","family":"Leedman","sequence":"additional","affiliation":[{"name":"Laboratory for Cancer Medicine, University of Western Australia Centre for Medical Research, Western Australian Institute for Medical Research and School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Huang","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, U.S.A."},{"name":"Conjugate and Medicinal Chemistry Laboratory, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine\u00a0M.","family":"Cahill","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2008,11,19]]},"reference":[{"key":"2021111720410819900_B1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nrn1537","article-title":"Iron, brain ageing and neurodegenerative disorders","volume":"5","author":"Zecca","year":"2004","journal-title":"Nat. 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