{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:23:32Z","timestamp":1760300612635,"version":"3.37.3"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2018-02503"],"award-info":[{"award-number":["2018-02503"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucopolysaccharidosis type I (MPS-I) is a rare lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase, which removes iduronic acid in both chondroitin\/dermatan sulfate (CS\/DS) and heparan sulfate (HS) and thereby contributes to the catabolism of glycosaminoglycans (GAGs). To ameliorate this genetic defect, the patients are currently treated by enzyme replacement and bone marrow transplantation, which have a number of drawbacks. This study was designed to develop an alternative treatment by inhibition of iduronic acid formation. By screening the Prestwick drug library, we identified ebselen as a potent inhibitor of enzymes that produce iduronic acid in CS\/DS and HS. Ebselen efficiently inhibited iduronic acid formation during CS\/DS synthesis in cultured fibroblasts. Treatment of MPS-I fibroblasts with ebselen not only reduced accumulation of CS\/DS but also promoted GAG degradation. In early Xenopus embryos, this drug phenocopied the effect of downregulation of DS-epimerase 1, the main enzyme responsible for iduronic production in CS\/DS, suggesting that ebselen inhibits iduronic acid production in vivo. However, ebselen failed to ameliorate the CS\/DS and GAG burden in MPS-I mice. Nevertheless, the results propose a potential of iduronic acid substrate reduction therapy for MPS-I patients.<\/jats:p>","DOI":"10.1093\/glycob\/cwab066","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:08:45Z","timestamp":1624619325000},"page":"1319-1329","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of iduronic acid biosynthesis by ebselen reduces glycosaminoglycan accumulation in mucopolysaccharidosis type I fibroblasts"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3549-8921","authenticated-orcid":false,"given":"Marco","family":"Maccarana","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, BMC B11, Uppsala University, Husargatan 3 Box 582 751 23 Uppsala, Sweden"},{"name":"Department of Experimental Medical Science, BMC C12, Lund University, BMC H11, 221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-9831","authenticated-orcid":false,"given":"Emil","family":"Tykesson","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, BMC C12, Lund University, BMC H11, 221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar M","family":"Pera","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, BMC H11, 221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nad\u00e8ge","family":"Gouignard","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, BMC H11, 221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1695-2693","authenticated-orcid":false,"given":"Jianping","family":"Fang","sequence":"additional","affiliation":[{"name":"GlycoNovo Technologies Co., Ltd., Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-146X","authenticated-orcid":false,"given":"Anders","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, BMC C12, Lund University, BMC H11, 221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Ghiselli","sequence":"additional","affiliation":[{"name":"Glyconova Srl, Parco Scientifico Silvano Fumero, Bioindustry Park Silvano Fumero S.p.A Via Ribes, 5 - 10010 - Colleretto Giacosa (TO), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, BMC B11, Uppsala University, Husargatan 3 Box 582 751 23 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"2021111808081598800_ref1","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.1007\/s11033-014-3417-x","article-title":"Ebselen, a promising antioxidant drug: mechanisms of action and targets of biological pathways","volume":"41","author":"Azad","year":"2014","journal-title":"Mol Biol Rep"},{"key":"2021111808081598800_ref2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00005-012-0195-9","article-title":"Putative biological mechanisms of efficiency of substrate reduction therapies for mucopolysaccharidoses","volume":"60","author":"Banecka-Majkutewicz","year":"2012","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"2021111808081598800_ref3","doi-asserted-by":"crossref","first-page":"e66704","DOI":"10.1371\/journal.pone.0066704","article-title":"Iduronic acid in chondroitin\/dermatan sulfate affects directional migration of aortic smooth muscle cells","volume":"8","author":"Bartolini","year":"2013","journal-title":"PLoS One"},{"key":"2021111808081598800_ref4","doi-asserted-by":"crossref","first-page":"26953","DOI":"10.1016\/S0021-9258(18)47111-6","article-title":"Biosynthesis of heparin\/heparan sulfate. 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