{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:24:45Z","timestamp":1790641485236,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T00:00:00Z","timestamp":1594080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CPII16\/00016"],"award-info":[{"award-number":["CPII16\/00016"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00916"],"award-info":[{"award-number":["PI17\/00916"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Biotin is an essential cofactor for carboxylases that regulates the energy metabolism. Recently, high\u2010dose pharmaceutical\u2010grade biotin (MD1003) was shown to improve clinical parameters in a subset of patients with chronic progressive multiple sclerosis. To gain insight into the mechanisms of action, we investigated the efficacy of high\u2010dose biotin in a genetic model of chronic axonopathy caused by oxidative damage and bioenergetic failure, the\n                    <jats:italic>\n                      Abcd1\n                      <jats:sup>\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mouse model of adrenomyeloneuropathy. High\u2010dose biotin restored redox homeostasis driven by NRF\u20102, mitochondria biogenesis and ATP levels, and reversed axonal demise and locomotor impairment. Moreover, we uncovered a concerted dysregulation of the transcriptional program for lipid synthesis and degradation in the spinal cord likely driven by aberrant SREBP\u20101c\/mTORC1signaling. This resulted in increased triglyceride levels and lipid droplets in motor neurons. High\u2010dose biotin normalized the hyperactivation of mTORC1, thus restoring lipid homeostasis. These results shed light into the mechanism of action of high\u2010dose biotin of relevance for neurodegenerative and metabolic disorders.\n                  <\/jats:p>","DOI":"10.1111\/bpa.12869","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T13:34:17Z","timestamp":1591623257000},"page":"945-963","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["High\u2010dose biotin restores redox balance, energy and lipid homeostasis, and axonal health in a model of adrenoleukodystrophy"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-5007","authenticated-orcid":false,"given":"St\u00e9phane","family":"Fourcade","sequence":"first","affiliation":[{"name":"Neurometabolic Diseases Laboratory IDIBELL Barcelona Spain"},{"name":"CIBERER U759 Center for Biomedical Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leire","family":"Goicoechea","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory IDIBELL Barcelona Spain"},{"name":"CIBERER U759 Center for Biomedical Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janani","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory IDIBELL Barcelona Spain"},{"name":"CIBERER U759 Center for Biomedical Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agatha","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory IDIBELL Barcelona Spain"},{"name":"CIBERER U759 Center for Biomedical Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Launay","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory IDIBELL Barcelona Spain"},{"name":"CIBERER U759 Center for Biomedical Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory IDIBELL Barcelona Spain"},{"name":"CIBERER U759 Center for Biomedical Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Seyer","sequence":"additional","affiliation":[{"name":"Medday Pharmaceuticals SA Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Colsch","sequence":"additional","affiliation":[{"name":"Service de Pharmacologie et Immuno\u2010Analyse (SPI) Laboratoire d'Etude du M\u00e9tabolisme des M\u00e9dicaments CEA INRA Universit\u00e9 Paris Saclay MetaboHUB Gif\u2010sur\u2010Yvette F\u201091191 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel Ylagan","family":"Calingasan","sequence":"additional","affiliation":[{"name":"Feil Family Brain and Mind Research Institute Weill Cornell Medical College New York NY 10065 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics IDIBELL Faculty of Medicine University of Barcelona L'Hospitalet de Llobregat Barcelona 08907 Spain"},{"name":"Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED) ISCIII Madrid Spain"},{"name":"Institute of Neurosciences University of Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Flint","family":"Beal","sequence":"additional","affiliation":[{"name":"Feil Family Brain and Mind Research Institute Weill Cornell Medical College New York NY 10065 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Sedel","sequence":"additional","affiliation":[{"name":"Medday Pharmaceuticals SA Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9606-0600","authenticated-orcid":false,"given":"Aurora","family":"Pujol","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory IDIBELL Barcelona Spain"},{"name":"CIBERER U759 Center for Biomedical Research on Rare Diseases Barcelona Spain"},{"name":"Catalan Institution of Research and Advanced Studies (ICREA) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056843"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.09.020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)33465-9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071714-034355"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171242"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-019-00735-2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.02.016"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201902061"},{"key":"e_1_2_9_10_1","volume-title":"Synthesis and Turnover of Myelin Phospholipids and Cholesterol","author":"DeWille JE","year":"1992"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0288-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20736"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1700554"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt361"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-51"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00390.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi384"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.05.041"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn085"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90736.2008"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq082"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.02.005"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3877"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.08.018"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413706111"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b01028"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.001"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080709"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.028"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.04.015"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.07.009"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1378-8"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1655-9"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.11.123"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-018-0094-5"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.12.008"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M900237-JLR200"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.12.019"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22363"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws292"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt186"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.17.9366"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn105"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00001.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.055"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-950-5_9"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-329235"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt143"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.20"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.1585"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/361726a0"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108655"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/121.7.1267"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.05.002"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.03.014"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.07.007"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh323"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.499"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708604"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2006.03.005"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-110866"},{"key":"e_1_2_9_63_1","first-page":"6861","article-title":"Altered glycolipid and glycerophospholipid signaling drive inflammatory cascades in adrenomyeloneuropathy","volume":"24","author":"Ruiz M","year":"2015","journal-title":"Hum Mol Genet"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr536"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.017"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2015.01.005"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-016-1023-8"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.91"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(88)90158-7"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1096-0"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516667568"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-9335(98)80121-0"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.11.013"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100616-060608"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.04.004"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.445445"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.06.001"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.10.002"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1974.tb04274.x"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbpa.12869","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.12869","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bpa.12869","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.12869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T16:34:24Z","timestamp":1693931664000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.12869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,7]]},"references-count":78,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/bpa.12869"],"URL":"https:\/\/doi.org\/10.1111\/bpa.12869","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,7]]},"assertion":[{"value":"2020-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}