{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T21:19:52Z","timestamp":1777324792341,"version":"3.51.4"},"reference-count":14,"publisher":"IMR Press","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-NS069454"],"award-info":[{"award-number":["R01-NS069454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100002108","name":"Friedreich\u2019s Ataxia Research Alliance","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Heart, dentate nucleus, and dorsal root ganglia (DRG) are targets of tissue damage in Friedreich ataxia (FA). This report summarizes the histology and histopathology of iron in the main tissues affected by FA. None of the affected anatomical sites reveals an elevation of total iron levels. In the myocardium, a small percentage of fibers shows iron-reactive granular inclusions. The accumulation of larger iron aggregates and fiber invasion cause necrosis and damage to the contractile apparatus. In the dentate nucleus, the principal FA-caused tissue injury is neuronal atrophy and grumose reaction. X-ray fluorescence mapping of iron in the dentate nucleus in FA shows retention of the metal in the center of the collapsed structure. Immunohistochemistry of ferritin, a surrogate marker of tissue iron, confirms strong expression in oligodendrocytes of the efferent white matter of the dentate nucleus and abundance of ferritin-positive microglia in the atrophic gray matter. Iron dysmetabolism in DRG is complex and consists of prominent expression of ferritin in hyperplastic satellite cells and residual nodules, also a loss of the iron export protein ferroportin from the cytoplasm of the remaining DRG nerve cells.<\/jats:p>","DOI":"10.31083\/j.jin2301004","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T08:25:08Z","timestamp":1705652708000},"source":"Crossref","is-referenced-by-count":12,"title":["Tissue Iron in Friedreich Ataxia"],"prefix":"10.31083","volume":"23","author":[{"given":"Arnulf H","family":"Koeppen","sequence":"first","affiliation":[{"name":"Research Service (151), VA Medical Center, Albany, NY 12208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Lamarche JB, C\u00f4t\u00e9 M, Lemieux B. The cardiomyopathy of Friedreich\u2019s ataxia morphological observations in 3 cases. The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques. 1980; 7: 389\u2013396.","DOI":"10.1017\/S0317167100022927"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Campuzano V, Montermini L, Molt\u00f2 MD, Pianese L, Coss\u00e9e M, Cavalcanti F, et al. Friedreich\u2019s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science (New York, N.Y.). 1996; 271: 1423\u20131427.","DOI":"10.1126\/science.271.5254.1423"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Maio N, Jain A, Rouault TA. Mammalian iron-sulfur cluster biogenesis: Recent insights into the roles of frataxin, acyl carrier protein and ATPase-mediated transfer to recipient proteins. Current Opinion in Chemical Biology. 2020; 55: 34\u201344.","DOI":"10.1016\/j.cbpa.2019.11.014"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Waldvogel D, van Gelderen P, Hallett M. Increased iron in the dentate nucleus of patients with Friedrich\u2019s ataxia. Annals of Neurology. 1999; 46: 123\u2013125.","DOI":"10.1002\/1531-8249(199907)46:1<123::AID-ANA19>3.0.CO;2-H"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Boddaert N, Le Quan Sang KH, R\u00f6tig A, Leroy-Willig A, Gallet S, Brunelle F, et al. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood. 2007; 110: 401\u2013408.","DOI":"10.1182\/blood-2006-12-065433"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Michael S, Petrocine SV, Qian J, Lamarche JB, Knutson MD, Garrick MD, et al. Iron and iron-responsive proteins in the cardiomyopathy of Friedreich\u2019s ataxia. Cerebellum (London, England). 2006; 5: 257\u2013267.","DOI":"10.1080\/14734220600913246"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Koeppen AH, Ramirez RL, Becker AB, Bjork ST, Levi S, Santambrogio P, et al. The pathogenesis of cardiomyopathy in Friedreich ataxia. PLoS ONE. 2015; 10: e0116396.","DOI":"10.1371\/journal.pone.0116396"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Perls M. Nachweis von Eisenoxyd in gewissen Pigmenten. Virchows Archiv fur Pathologische Anatomie und Physiologie und f\u00fcr Klinische Medizin. 1867; 39: 42\u201348. (In German)","DOI":"10.1515\/9783112391884-004"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Koeppen AH, Michael SC, Knutson MD, Haile DJ, Qian J, Levi S, et al. The dentate nucleus in Friedreich\u2019s ataxia: the role of iron-responsive proteins. Acta Neuropathologica. 2007; 114: 163\u2013173.","DOI":"10.1007\/s00401-007-0220-y"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Koeppen AH, Ramirez RL, Yu D, Collins SE, Qian J, Parsons PJ, et al. Friedreich\u2019s ataxia causes redistribution of iron, copper, and zinc in the dentate nucleus. Cerebellum (London, England). 2012; 11: 845\u2013860.","DOI":"10.1007\/s12311-012-0383-5"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Spatz H. \u00dcber den Eisennachweis im Gehirn, besonders in Zentren des extrapyramidal-motorischen Systems. Zeitschrift f\u00fcr die gesamte Neurologie und Psychiatrie.1922; 77: 261\u2013390. (In German)","DOI":"10.1007\/BF02865844"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Koeppen AH, Becker AB, Qian J, Feustel PJ. Friedreich Ataxia: Hypoplasia of Spinal Cord and Dorsal Root Ganglia. Journal of Neuropathology and Experimental Neurology. 2017; 76: 101\u2013108.","DOI":"10.1093\/jnen\/nlw111"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Koeppen AH, Morral JA, Davis AN, Qian J, Petrocine SV, Knutson MD, et al. The dorsal root ganglion in Friedreich\u2019s ataxia. Acta Neuropathologica. 2009; 118: 763\u2013776.","DOI":"10.1007\/s00401-009-0589-x"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Koeppen AH, Kuntzsch EC, Bjork ST, Ramirez RL, Mazurkiewicz JE, Feustel PJ. Friedreich ataxia: metal dysmetabolism in dorsal root ganglia. Acta Neuropathologica Communications. 2013; 1: 26.","DOI":"10.1186\/2051-5960-1-26"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/23\/1\/10.31083\/j.jin2301004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T16:12:18Z","timestamp":1732723938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/23\/1\/10.31083\/j.jin2301004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,10]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024]]}},"alternative-id":["S0219-6352(23)00621-6"],"URL":"https:\/\/doi.org\/10.31083\/j.jin2301004","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,10]]},"article-number":"4"}}