{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:03:19Z","timestamp":1791147799937,"version":"4.1.0"},"reference-count":62,"publisher":"The Royal Society","issue":"1433","license":[{"start":{"date-parts":[[2003,5,29]],"date-time":"2003-05-29T00:00:00Z","timestamp":1054166400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phil. Trans. R. Soc. Lond. B"],"published-print":{"date-parts":[[2003,5,29]]},"abstract":"<jats:p>Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease\u2013related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions.<\/jats:p>\n                  <jats:p>\n                    An alternative therapeutic approach termed \u2018substrate deprivation\u2019 or \u2018substrate reduction therapy\u2019 (SRT) aims to balance cellular GSL biosynthesis with the impairment in catalytic activity seen in lysosomal storage disorders. The development of N\u2013alkylated iminosugars that have inhibitory activity against the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic cells, ceramide\u2013specific glucosyltransferase, offers a generic therapeutic for the treatment of all glucosphingolipidoses. The successful use of N\u2013alkylated iminosugars to establish SRT as an alternative therapeutic strategy has been demonstrated in\n                    <jats:italic>in vitro<\/jats:italic>\n                    ,\n                    <jats:italic>in vivo<\/jats:italic>\n                    and in clinical trials for type 1 Gaucher disease. The implications of these studies and the prospects of improvement to the design of iminosugar compounds for treating Gaucher and other GSL lysosomal storage disorders will be discussed.\n                  <\/jats:p>","DOI":"10.1098\/rstb.2003.1278","type":"journal-article","created":{"date-parts":[[2003,9,9]],"date-time":"2003-09-09T11:27:32Z","timestamp":1063106852000},"page":"927-945","source":"Crossref","is-referenced-by-count":58,"title":["Small\u2013molecule therapeutics for the treatment of glycolipid lysosomal storage disorders"],"prefix":"10.1098","volume":"358","author":[{"given":"Terry D.","family":"Butters","sequence":"first","affiliation":[{"name":"Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard R.","family":"Mellor","sequence":"additional","affiliation":[{"name":"Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Narita","sequence":"additional","affiliation":[{"name":"Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond A.","family":"Dwek","sequence":"additional","affiliation":[{"name":"Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2003,5,29]]},"reference":[{"key":"p_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(95)00217-0"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00384-6"},{"key":"p_3","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/S0021-9258(19)44311-1","article-title":"Enzymatic synthesis of glucocerebroside by a glucosyltransferase from embryonic chicken brain","volume":"248","author":"Basu S.","year":"1973","journal-title":"J. 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