{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:24:05Z","timestamp":1778624645177,"version":"3.51.4"},"reference-count":42,"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>Glycosphingolipids are a polysaccharide chain between 1 and 40 carbohydrate residues long glycosidically linked to ceramide (a long\u2013chain aliphatic amino\u2013alcohol or sphingoid) that is embedded in the cell plasma membrane with the carbohydrate moiety on the outside. The sphingoid imparts rigidity to the membrane and the carbohydrate tails protect the cell surface and have functions in relation to cell adhesion, growth, regulation, differentiation, cell interaction, recognition and signalling. They provide adhesion sites for pathogens and change during oncogenic transformation. Ceramide is also a component of sphingomyelin. Glycosphingolipids are degraded by lysosomal hydrolysis. The sphingolipidoses are a series of diseases in which mutations affecting the enzymes catalysing the last 11 steps of this process causing abnormal compounds proximal to the metabolic block to accumulate intralysosomally. Thus, they are a sub\u2013group of the lysosomal storage diseases. The degradation of sphingolipids containing three or less carbohydrate residues requires a sphingolipid activator protein and mutations affecting these proteins also cause abnormal glycosphingolipid storage.<\/jats:p>\n                  <jats:p>\n                    With one exception (Fabry disease, which is X linked) the sphingolipidoses are inherited autosomally. The phenotypic manifestations of the individual sphingolipidoses are variable although the more severe variants are usually the better known. They have generally been regarded as untreatable but notable therapeutic advances are being made by enzyme replacement therapy and regulating the rate of glycosphingolipid synthesis by inhibiting UDP\u2013glucose\u2013\n                    <jats:italic>N<\/jats:italic>\n                    \u2013acylsphingosine D\u2013glucosyl transferase (CerGlcT), which is the first reaction on the pathway of glycosphingolipid synthesis. The compounds used are N\u2013alkylated iminosugars whose glucose and galactose stereochemistries inhibit CerGlcT.\n                  <\/jats:p>\n                  <jats:p>Prenatal and carrier state diagnosis, genetic counselling and the abortion of affected foetuses are reducing the incidence of some of the most severe sphingolipidoses in certain high\u2013incidence populations.<\/jats:p>","DOI":"10.1098\/rstb.2003.1280","type":"journal-article","created":{"date-parts":[[2003,9,9]],"date-time":"2003-09-09T11:27:32Z","timestamp":1063106852000},"page":"975-983","source":"Crossref","is-referenced-by-count":5,"title":["A historical perspective of the glycosphingolipids and sphingolipidoses"],"prefix":"10.1098","volume":"358","author":[{"given":"Richard W. E.","family":"Watts","sequence":"first","affiliation":[{"name":"Department of Medicine, Imperial College of Science, Technology and Medicine (Hammersmith Campus), Hammersmith Hospital, Du Cane Road, London W12 0HS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2003,5,29]]},"reference":[{"key":"p_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2003.1273"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg910"},{"key":"p_3","unstructured":"Barranger J. A. & Brady R. O. (eds) 1984 Molecular basis of lysosomal storage diseases. 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Liss."},{"key":"p_22","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s004180100286","article-title":"Lysosomal sulfoglycolipid storage in the kidneys of mice deficient in arylsulfatase A (ASA) and of double-knockout mice deficient for ASA and galactoceramide synthase","volume":"116","author":"Lullman-Rauch R.","year":"2001","journal-title":"Histochem. Cell Biol."},{"key":"p_23","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2003.1271"},{"key":"p_24","doi-asserted-by":"crossref","unstructured":"Neufeld E. d'Azzo A. & Proinia R. L. 1984 Defective synthesis or maturation of the a-chain of b-hexosamidase in classic and variant forms of Tay-Sachs disease. In Molecular basis of Iysosomal storage disorders (ed. J. A. Barranger & R. O. Brady) pp. 251-256. 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