{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:51:34Z","timestamp":1789865494162,"version":"4.0.1"},"reference-count":62,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","medical-hypotheses.com","clinicalkey.com","clinicalkey.es","clinicalkey.fr","clinicalkey.com.au","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Medical Hypotheses"],"published-print":{"date-parts":[[2017,9]]},"DOI":"10.1016\/j.mehy.2017.07.022","type":"journal-article","created":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T18:31:52Z","timestamp":1500575512000},"page":"51-54","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Hepcidin and metallothioneins as molecular base for sex-dependent differences in clinical course of experimental autoimmune encephalomyelitis in chronic iron overload"],"prefix":"10.1016","volume":"107","author":[{"given":"Bo\u017eena","family":"\u0106urko-Cofek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Grubi\u0107 Kezele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Barac-Latas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mehy.2017.07.022_b0005","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3389\/fimmu.2015.00647","article-title":"Multiple sclerosis between genetics and infections: human endogenous retroviruses in monocytes and macrophages","volume":"6","author":"Morandi","year":"2015","journal-title":"Front Immunol"},{"key":"10.1016\/j.mehy.2017.07.022_b0010","first-page":"15","article-title":"Overview of the epidemiology, diagnosis, and disease progression associated with multiple sclerosis","volume":"19","author":"Tullman","year":"2013","journal-title":"Am J Manag Care"},{"key":"10.1016\/j.mehy.2017.07.022_b0015","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1055\/s-0036-1579693","article-title":"Epidemiology of multiple sclerosis: from risk factors to prevention-an update","volume":"36","author":"Ascherio","year":"2016","journal-title":"Semin Neurol"},{"key":"10.1016\/j.mehy.2017.07.022_b0020","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1056\/NEJM200009283431307","article-title":"Multiple sclerosis","volume":"343","author":"Noseworthy","year":"2000","journal-title":"N Engl J Med"},{"key":"10.1016\/j.mehy.2017.07.022_b0025","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/QCO.0b013e3282f88b48","article-title":"Multiple sclerosis: immunopathogenesis and controversies in defining the cause","volume":"21","author":"Holm\u00f8y","year":"2008","journal-title":"Curr Opin Infect Dis"},{"key":"10.1016\/j.mehy.2017.07.022_b0030","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S1474-4422(10)70094-6","article-title":"Multiple sclerosis: risk factors, prodromes, and potential causal pathways","volume":"9","author":"Ramagopalan","year":"2010","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.mehy.2017.07.022_b0035","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/ana.20820","article-title":"Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis","volume":"59","author":"Thacker","year":"2006","journal-title":"Ann Neurol"},{"key":"10.1016\/j.mehy.2017.07.022_b0040","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S1474-4422(10)70086-7","article-title":"Vitamin D and multiple sclerosis","volume":"9","author":"Ascherio","year":"2010","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.mehy.2017.07.022_b0045","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1177\/1352458506073501","article-title":"Smoking is a risk factor for multiple sclerosis: a metanalysis","volume":"13","author":"Hawkes","year":"2007","journal-title":"Mult Scler"},{"key":"10.1016\/j.mehy.2017.07.022_b0050","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000342779","article-title":"Incidence and prevalence of multiple sclerosis in the Americas: a systematic review","volume":"40","author":"Evans","year":"2013","journal-title":"Neuroepidemiology"},{"key":"10.1016\/j.mehy.2017.07.022_b0055","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.spen.2006.08.002","article-title":"Brain iron metabolism","volume":"13","author":"Rouault","year":"2006","journal-title":"Semin Pediatr Neurol"},{"key":"10.1016\/j.mehy.2017.07.022_b0060","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.pneurobio.2007.07.009","article-title":"Brain iron metabolism: neurobiology and neurochemistry","volume":"83","author":"Ke","year":"2007","journal-title":"Prog Neurobiol"},{"key":"10.1016\/j.mehy.2017.07.022_b0065","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1148\/radiol.11110601","article-title":"Chronic multiple sclerosis lesions: characterization with high field strength MR imaging","volume":"262","author":"Yao","year":"2012","journal-title":"Radiology"},{"key":"10.1016\/j.mehy.2017.07.022_b0070","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00441-004-0976-5","article-title":"Redox imbalance","volume":"318","author":"Berg","year":"2004","journal-title":"Cell Tissue Res"},{"key":"10.1016\/j.mehy.2017.07.022_b0075","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.micinf.2011.10.001","article-title":"Iron metabolism and the innate immune response to infection","volume":"14","author":"Johnson","year":"2012","journal-title":"Microbes Infect"},{"key":"10.1016\/j.mehy.2017.07.022_b0080","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/1096-8652(200008)64:4<287::AID-AJH9>3.0.CO;2-L","article-title":"Iron absorbtion and transport: an update","volume":"64","author":"Conrad","year":"2000","journal-title":"Am J Hematol"},{"key":"10.1016\/j.mehy.2017.07.022_b0085","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3945\/jn.110.127639","article-title":"Iron homeostasis and nutritional iron deficiency","volume":"141","author":"Theil","year":"2011","journal-title":"J. Nutr"},{"key":"10.1016\/j.mehy.2017.07.022_b0090","first-page":"5","article-title":"Normal iron metabolism and the pathophysiology of iron overload disorders","volume":"27","author":"Siah","year":"2006","journal-title":"Clin Biochem Rev"},{"key":"10.1016\/j.mehy.2017.07.022_b0095","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1042\/BJ20101825","article-title":"Regulation of cellular iron metabolism","volume":"434","author":"Wang","year":"2011","journal-title":"Biochem J"},{"key":"10.1016\/j.mehy.2017.07.022_b0100","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1113\/jphysiol.2003.049478","article-title":"Mitochondrial formation of reactive oxygen species","volume":"552","author":"Turrens","year":"2003","journal-title":"J Physiol"},{"key":"10.1016\/j.mehy.2017.07.022_b0105","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1471-2202-13-79","article-title":"Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia","volume":"13","author":"Mehta","year":"2012","journal-title":"BMC Neurosci"},{"key":"10.1016\/j.mehy.2017.07.022_b0110","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/MAJ.0b013e318271c031","article-title":"Induction of autophagic cell death in the rat brain caused by iron","volume":"345","author":"Chen","year":"2013","journal-title":"Am J Med Sci"},{"key":"10.1016\/j.mehy.2017.07.022_b0115","doi-asserted-by":"crossref","first-page":"13301","DOI":"10.1523\/JNEUROSCI.2838-11.2011","article-title":"Iron efflux from oligodendrocytes is differentially regulated in gray and white matter","volume":"31","author":"Schulz","year":"2011","journal-title":"J Neurosci"},{"key":"10.1016\/j.mehy.2017.07.022_b0120","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/glia.20784","article-title":"Oligodendrocytes and myelination: the role of iron","volume":"57","author":"Todorich","year":"2009","journal-title":"Glia"},{"key":"10.1016\/j.mehy.2017.07.022_b0125","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1097\/00004647-200011000-00002","article-title":"The lipid peroxidation by-product 4-hydroxynonenal is toxic to axons and oligodendrocytes","volume":"20","author":"McCracken","year":"2000","journal-title":"J Cereb Blood Flow and Metab"},{"key":"10.1016\/j.mehy.2017.07.022_b0130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuro.2016.08.014","article-title":"Chronic iron overload induces gender-dependent changes in iron homeostasis, lipid peroxidation and clinical course of experimental autoimmune encephalomyelitis","volume":"57","author":"\u0106urko-Cofek","year":"2016","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.mehy.2017.07.022_b0135","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1476-5381.2011.01302.x","article-title":"Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)","volume":"164","author":"Constantinescu","year":"2011","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.mehy.2017.07.022_b0140","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0165-5728(95)00153-0","article-title":"Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis in DA rats immunized with syngeneic spinal cord and incomplete Freund's adjuvant","volume":"63","author":"Lorentzen","year":"1995","journal-title":"J Neuroimmunol"},{"key":"10.1016\/j.mehy.2017.07.022_b0145","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJM200011163432001","article-title":"Relapses and progression of disability in multiple sclerosis","volume":"343","author":"Confavreux","year":"2000","journal-title":"N Engl J Med"},{"key":"10.1016\/j.mehy.2017.07.022_b0150","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/ana.20913","article-title":"How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis","volume":"60","author":"Steinman","year":"2006","journal-title":"Ann. Neurol"},{"key":"10.1016\/j.mehy.2017.07.022_b0155","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.bbagen.2011.07.014","article-title":"Non-transferrin bound iron: A key role in iron overload and iron toxicity","volume":"1820","author":"Brissot","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.mehy.2017.07.022_b0160","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.gene.2012.09.060","article-title":"Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element","volume":"511","author":"Hou","year":"2012","journal-title":"Gene"},{"key":"10.1016\/j.mehy.2017.07.022_b0165","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jtemb.2005.03.003","article-title":"Advances in metallothionein structure and functions","volume":"19","author":"Va\u0161ak","year":"2005","journal-title":"J Trace Elem Med Biol"},{"key":"10.1016\/j.mehy.2017.07.022_b0170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-5793(96)00356-0","article-title":"Reversible zinc exchange between metallothionein and the estrogen receptor zinc finger","volume":"386","author":"Cano-Gauci","year":"1996","journal-title":"FEBS Lett"},{"key":"10.1016\/j.mehy.2017.07.022_b0175","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1182\/blood-2011-01-258467","article-title":"Hepcidin and iron regulation, 10years later","volume":"117","author":"Ganz","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.mehy.2017.07.022_b0180","doi-asserted-by":"crossref","first-page":"7806","DOI":"10.1074\/jbc.M008922200","article-title":"Hepcidin, a urinary antimicrobial peptide synthesized in the liver","volume":"276","author":"Park","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.mehy.2017.07.022_b0185","first-page":"9","article-title":"Fisiopathology of iron metabolism: diagnostic and therapeutic implications","volume":"25","author":"Mu\u00f1oz G\u00f3mez","year":"2005","journal-title":"Nefrologia"},{"key":"10.1016\/j.mehy.2017.07.022_b0190","first-page":"124","article-title":"Hepcidin and its role in iron homeostasis","volume":"20","author":"Kwapisz","year":"2009","journal-title":"EJIFCC"},{"key":"10.1016\/j.mehy.2017.07.022_b0195","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization","volume":"306","author":"Nemeth","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.mehy.2017.07.022_b0200","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1053\/j.gastro.2010.12.037","article-title":"Intestinal DMT1 cotransporter is down-regulated by hepcidin via proteasome internalization and degradation","volume":"140","author":"Brasse-Lagnel","year":"2011","journal-title":"Gastroenterol"},{"key":"10.1016\/j.mehy.2017.07.022_b0205","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3324\/haematol.2009.014399","article-title":"Hepcidin targets ferroportin for degradation in hepatocytes","volume":"95","author":"Ramey","year":"2010","journal-title":"Haematologica"},{"key":"10.1016\/j.mehy.2017.07.022_b0210","doi-asserted-by":"crossref","first-page":"48775","DOI":"10.1074\/jbc.M105392200","article-title":"Iron prevents ferritin turnover in hepatic cells","volume":"276","author":"Truty","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.mehy.2017.07.022_b0215","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1172\/JCI0215686","article-title":"The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation","volume":"110","author":"Nicolas","year":"2002","journal-title":"J Clin Invest"},{"key":"10.1016\/j.mehy.2017.07.022_b0220","doi-asserted-by":"crossref","first-page":"e40465","DOI":"10.1371\/journal.pone.0040465","article-title":"Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes","volume":"7","author":"Ikeda","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.mehy.2017.07.022_b0225","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1182\/asheducation-2006.1.29","article-title":"Hepcidin and its role in regulating systemic iron metabolism","author":"Ganz","year":"2006","journal-title":"Hematology"},{"key":"10.1016\/j.mehy.2017.07.022_b0230","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bcmd.2007.01.004","article-title":"In vivo imaging of hepcidin promoter stimulation by iron and inflammation","volume":"38","author":"Flanagan","year":"2007","journal-title":"Blood Cells Mol Dis"},{"key":"10.1016\/j.mehy.2017.07.022_b0235","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1172\/JCI83831","article-title":"Progesterone receptor membrane component-1 regulates hepcidin biosynthesis","volume":"126","author":"Li","year":"2016","journal-title":"J Clin Invest"},{"key":"10.1016\/j.mehy.2017.07.022_b0240","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/acel.12052","article-title":"Testosterone administration inhibits hepcidin transcription and is associated with increased iron incorporation into red blood cells","volume":"12","author":"Guo","year":"2013","journal-title":"Aging Cell"},{"key":"10.1016\/j.mehy.2017.07.022_b0245","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1016\/j.jinorgbio.2006.09.005","article-title":"Metal-dependent protein folding: metallation of metallothionein","volume":"100","author":"Rigby Duncan","year":"2006","journal-title":"J Inorg Biochem"},{"key":"10.1016\/j.mehy.2017.07.022_b0250","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jtemb.2007.09.011","article-title":"Metallothionein functions and structural characteristics","volume":"21","author":"Carpene","year":"2007","journal-title":"J Trace Elem Med Biol"},{"key":"10.1016\/j.mehy.2017.07.022_b0255","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/jn\/130.5.1085","article-title":"Metallothionein expression in animals: a physiological perspective on function","volume":"130","author":"Davis","year":"2000","journal-title":"J Nutr"},{"key":"10.1016\/j.mehy.2017.07.022_b0260","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<60::AID-PATH387>3.0.CO;2-J","article-title":"Metallothionein expression and nuclear size in benign, borderline, and malignant serous ovarian tumours","volume":"189","author":"Tan","year":"1999","journal-title":"J Pathol"},{"key":"10.1016\/j.mehy.2017.07.022_b0265","doi-asserted-by":"crossref","first-page":"993","DOI":"10.3748\/wjg.v13.i7.993","article-title":"Metallothionein: an overview","volume":"13","author":"Thirumoorthy","year":"2007","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.mehy.2017.07.022_b0270","doi-asserted-by":"crossref","first-page":"6044","DOI":"10.3390\/ijms14036044","article-title":"The role of metallothionein in oxidative stress","volume":"14","author":"Ruttkay-Nedecky","year":"2013","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.mehy.2017.07.022_b0275","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1387-3806(00)00343-2","article-title":"Stoichiometry in zinc ion transfer from metallothionein to zinc finger peptides","volume":"204","author":"Hathout","year":"2001","journal-title":"Int. J Mass Spectrom"},{"key":"10.1016\/j.mehy.2017.07.022_b0280","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00335-010-9257-7","article-title":"Comparative analysis of MTF-1 binding sites between human and mouse","volume":"21","author":"Wang","year":"2010","journal-title":"Mamm Genome"},{"key":"10.1016\/j.mehy.2017.07.022_b0285","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0006-2952(99)00301-9","article-title":"Regulation of metallothionein gene expression by oxidative stress and metal ions","volume":"59","author":"Andrews","year":"2000","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.mehy.2017.07.022_b0290","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/348458a0","article-title":"Solution structure of the DNA binding domain of the oestrogen receptor","volume":"348","author":"Schwabe","year":"1990","journal-title":"Nature"},{"key":"10.1016\/j.mehy.2017.07.022_b0295","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.1074\/jbc.271.9.5125","article-title":"In vivo and in vitro iron-replaced zinc finger generates free radicals and causes DNA damage","volume":"271","author":"Conte","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/j.mehy.2017.07.022_b0300","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.clim.2013.03.005","article-title":"Sexual disparities in the incidence and course of MS","volume":"149","author":"Bove","year":"2013","journal-title":"Clinical Immunology"},{"key":"10.1016\/j.mehy.2017.07.022_b0305","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1177\/1352458511422097","article-title":"Temporal trends of disability progression in multiple sclerosis: findings from British Columbia, Canada (1975-2009)","volume":"18","author":"Shirani","year":"2012","journal-title":"Mult Scler J"},{"key":"10.1016\/j.mehy.2017.07.022_b0310","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1212\/WNL.0b013e31821e559d","article-title":"Demographic and clinical characteristics of malignant multiple sclerosis","volume":"76","author":"Gholipour","year":"2011","journal-title":"Neurology"}],"container-title":["Medical Hypotheses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306987717300968?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306987717300968?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T03:20:56Z","timestamp":1535599256000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306987717300968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":62,"alternative-id":["S0306987717300968"],"URL":"https:\/\/doi.org\/10.1016\/j.mehy.2017.07.022","relation":{},"ISSN":["0306-9877"],"issn-type":[{"value":"0306-9877","type":"print"}],"subject":[],"published":{"date-parts":[[2017,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hepcidin and metallothioneins as molecular base for sex-dependent differences in clinical course of experimental autoimmune encephalomyelitis in chronic iron overload","name":"articletitle","label":"Article Title"},{"value":"Medical Hypotheses","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mehy.2017.07.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}