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The lysosomal system regulates key aspects of iron homeostasis, which prompted us to investigate whether there are hematological abnormalities and iron metabolism defects in NPC1.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods<\/ns4:bold>\n                    : Iron-related hematological parameters, systemic and tissue metal ion and relevant hormonal and proteins levels, expression of specific pro-inflammatory mediators and erythrophagocytosis were evaluated in an authentic mouse model and in a large cohort of NPC patients.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results<\/ns4:bold>\n                    : Significant changes in mean corpuscular volume and corpuscular hemoglobin were detected in\n                    <ns4:italic>Npc1<\/ns4:italic>\n                    <ns4:sup>-\/-<\/ns4:sup>\n                    mice from an early age. Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron deficiency, increased circulating hepcidin, decreased ferritin and abnormal pro-inflammatory cytokine levels were also found. Furthermore, there is evidence of defective erythrophagocytosis in\n                    <ns4:italic>Npc1<\/ns4:italic>\n                    <ns4:sup>-\/-<\/ns4:sup>\n                    mice and in an\n                    <ns4:italic>in vitro<\/ns4:italic>\n                    NPC1 cellular model. Comparable hematological changes, including low normal serum iron and transferrin saturation and low cerebrospinal fluid\u00a0ferritin were confirmed in NPC1 patients.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions<\/ns4:bold>\n                    : These data suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.17261.2","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T10:45:05Z","timestamp":1680518705000},"page":"267","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Defective iron homeostasis and hematological abnormalities in Niemann-Pick disease type C1"],"prefix":"10.12688","volume":"7","author":[{"given":"Oscar C 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Hentze","year":"2010","journal-title":"Cell."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"623-635","DOI":"10.1038\/nrm2745","article-title":"Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function.","volume":"10","author":"P Saftig","year":"2009","journal-title":"Nat Rev Mol Cell Biol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"105-109","DOI":"10.1038\/nature13148","article-title":"Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy.","volume":"509","author":"J Mancias","year":"2014","journal-title":"Nature."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1755-1758","DOI":"10.1172\/JCI32701","article-title":"Hepcidin regulation: ironing out the details.","volume":"117","author":"I De Domenico","year":"2007","journal-title":"J Clin Invest."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"2826-2832","DOI":"10.1016\/j.biocel.2008.05.015","article-title":"A role for 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Loftus","year":"1997","journal-title":"Science."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"3164-3169","DOI":"10.1073\/pnas.1422373112","article-title":"Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function.","volume":"112","author":"S Lakhal-Littleton","year":"2015","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"4259-4267","DOI":"10.1182\/blood-2008-03-143008","article-title":"CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcgamma receptor-mediated but not scavenger receptor-mediated recognition by macrophages.","volume":"112","author":"M Olsson","year":"2008","journal-title":"Blood."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"132-140","DOI":"10.1002\/ajmg.b.30969","article-title":"Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C.","volume":"153B","author":"N Yanjanin","year":"2010","journal-title":"Am J Med Genet B Neuropsychiatr Genet."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"e00192","DOI":"10.1042\/BSR20150014","article-title":"Hepcidin: regulation of the master iron regulator.","volume":"35","author":"G Rishi","year":"2015","journal-title":"Biosci Rep."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"e12177","DOI":"10.7554\/eLife.12177","article-title":"Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection.","volume":"4","author":"F Lu","year":"2015","journal-title":"eLife."},{"key":"ref-30","article-title":"Pediatric Reference Intervals.","author":"S Soldin","year":"2011"},{"key":"ref-31","article-title":"The Harriet Lane Handbook.","author":"H Hughes","year":"2017"},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"599-610","DOI":"10.1038\/nrgastro.2010.151","article-title":"Diagnosis and management of iron deficiency anemia in patients with IBD.","volume":"7","author":"J Stein","year":"2010","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"1527-1539","DOI":"10.1039\/c4mt00056k","article-title":"Hepatic metabolic response to restricted copper intake in a Niemann-Pick C murine model.","volume":"6","author":"G Arg\u00fcello","year":"2014","journal-title":"Metallomics."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"542-553","DOI":"10.1039\/c3mt00308f","article-title":"Altered transition metal homeostasis in Niemann-Pick disease, type C1.","volume":"6","author":"Y Hung","year":"2014","journal-title":"Metallomics."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"196-202","DOI":"10.1006\/mgme.2000.3004","article-title":"Deficient ferritin immunoreactivity in tissues from niemann-pick type C patients: extension of findings to fetal tissues, H and L ferritin isoforms, but also one case of the rare Niemann-Pick C2 complementation 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Goodnough","year":"2010","journal-title":"Blood."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"420-423","DOI":"10.1136\/practneurol-2019-002236","article-title":"Niemann-Pick type C: contemporary diagnosis and treatment of a classical disorder.","volume":"19","author":"M Lad","year":"2019","journal-title":"Pract Neurol."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"93-130","DOI":"10.1080\/10408360091174196","article-title":"Reticulocyte cellular indices: a new approach in the diagnosis of anemias and monitoring of erythropoietic function.","volume":"37","author":"C Brugnara","year":"2000","journal-title":"Crit Rev Clin Lab Sci."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"1066-1076","DOI":"10.1093\/clinchem\/48.7.1066","article-title":"Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency.","volume":"48","author":"C Thomas","year":"2002","journal-title":"Clin Chem."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"1271-1276","DOI":"10.1172\/JCI20945","article-title":"IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.","volume":"113","author":"E Nemeth","year":"2004","journal-title":"J Clin Invest."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"1879-1891","DOI":"10.1523\/JNEUROSCI.5282-06.2007","article-title":"Endosomal accumulation of Toll-like receptor 4 causes constitutive secretion of cytokines and activation of signal transducers and activators of transcription in Niemann-Pick disease type C (NPC) fibroblasts: a potential basis for glial cell activation in the NPC brain.","volume":"27","author":"M Suzuki","year":"2007","journal-title":"J Neurosci."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"e51031","DOI":"10.7554\/eLife.51031","article-title":"Impaired lysosomal acidification triggers iron deficiency and inflammation in 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Disease: An In-Depth Review.","volume":"26","author":"A Madu","year":"2017","journal-title":"Med Princ Pract."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"406-416","DOI":"10.1016\/j.nbd.2009.01.015","article-title":"Critical role of iron in the pathogenesis of the murine gangliosidoses.","volume":"34","author":"M Jeyakumar","year":"2009","journal-title":"Neurobiol Dis."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1097\/HS9.0000000000000035","article-title":"Erythroferrone: An Erythroid Regulator of Hepcidin and Iron Metabolism.","volume":"2","author":"R Coffey","year":"2018","journal-title":"Hemasphere."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41572-018-0025-4","article-title":"Lysosomal storage diseases.","volume":"4","author":"F Platt","year":"2018","journal-title":"Nat Rev Dis Primers."},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"17413-17418","DOI":"10.1073\/pnas.0909296106","article-title":"Resolving the distinct stages in erythroid differentiation based on dynamic changes in membrane protein expression during erythropoiesis.","volume":"106","author":"K Chen","year":"2009","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-53","doi-asserted-by":"publisher","first-page":"945-951","DOI":"10.1038\/nm.4146","article-title":"On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.","volume":"22","author":"I Theurl","year":"2016","journal-title":"Nat Med."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"87-95","DOI":"10.1007\/s10534-020-00233-5","article-title":"Iron chelation by deferiprone does not rescue the Niemann-Pick Disease Type C1 mouse model.","volume":"33","author":"Y Hung","year":"2020","journal-title":"Biometals."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"863-873","DOI":"10.1038\/nrn1537","article-title":"Iron, brain ageing and neurodegenerative disorders.","volume":"5","author":"L Zecca","year":"2004","journal-title":"Nat Rev Neurosci."},{"key":"ref-56","doi-asserted-by":"publisher","first-page":"378278","DOI":"10.1155\/2011\/378278","article-title":"Dysregulation of iron metabolism in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.","volume":"2011","author":"S Oshiro","year":"2011","journal-title":"Adv Pharmacol Sci."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"695-703","DOI":"10.1007\/s00702-012-0922-8","article-title":"Excess iron harms the brain: the syndromes of neurodegeneration with brain iron accumulation (NBIA).","volume":"120","author":"S Schneider","year":"2013","journal-title":"J Neural Transm 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.21047.r56003, Frank W. Pfrieger, Centre National de la Recherche Scientifique, Institute of Cellular and Integrative Neurosciences, Universite de Strasbourg, Strasbourg, Grand Est, 03 Apr 2023, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/7-267\/v2#referee-response-56003","order":0,"name":"referee-response-56003","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.21047.r56002, Caroline Hastings, Department of Pediatrics, Division of Hematology Oncology, Benioff Children's Hospital Oakland, University of California San Francisco, Oakland, CA, 11 Apr 2023, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/7-267\/v2#referee-response-56002","order":1,"name":"referee-response-56002","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [202834, <a href=https:\/\/doi.org\/10.35802\/202834>https:\/\/doi.org\/10.35802\/202834<\/a>; an Investigator Award in Science award to F.M.P.]. F.M.P. received grants from CLIMB (Children Living with Inherited Metabolic Diseases, United Kingdom), Niemann-Pick Research Foundation (NPRF, United Kingdom), Action Medical Research (AMR, United Kingdom) and the John Fell Foundation (University of Oxford). O.C-W.C. was supported by The Clarendon Fund (Clarendon Foundation, University of Oxford) and the Jason Hu scholarship (Balliol College, University of Oxford). E-R. N. was funded by Action Medical Research, UK. D. S. and N.P. were funded by Wellcome. F.D.P. received support from the Ara Parseghian Medical Research Foundation (N.Y.F), Therapeutics for Rare and Neglected Diseases program, Bench to Bedside award from the Office of Rare Diseases, and the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. F.M.P. is a Royal Society Wolfson Research Merit Award holder. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}