Publication Date:
1997-04-18
Description:
The glycosphingolipid (GSL) lysosomal storage diseases result from the inheritance of defects in the genes encoding the enzymes required for catabolism of GSLs within lysosomes. A strategy for the treatment of these diseases, based on an inhibitor of GSL biosynthesis N-butyldeoxynojirimycin, was evaluated in a mouse model of Tay-Sachs disease. When Tay-Sachs mice were treated with N-butyldeoxynojirimycin, the accumulation of GM2 in the brain was prevented, with the number of storage neurons and the quantity of ganglioside stored per cell markedly reduced. Thus, limiting the biosynthesis of the substrate (GM2) for the defective enzyme (beta-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Platt, F M -- Neises, G R -- Reinkensmeier, G -- Townsend, M J -- Perry, V H -- Proia, R L -- Winchester, B -- Dwek, R A -- Butters, T D -- New York, N.Y. -- Science. 1997 Apr 18;276(5311):428-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford 0X1 3QU, UK. fran@oxglua.glycob.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9103204" target="_blank"〉PubMed〈/a〉
Keywords:
1-Deoxynojirimycin/*analogs & derivatives/pharmacokinetics/therapeutic use
;
Animals
;
Blood-Brain Barrier
;
Brain/*metabolism
;
Disease Models, Animal
;
Enzyme Inhibitors/*therapeutic use
;
G(M2) Ganglioside/biosynthesis/*metabolism
;
Lysosomes/*metabolism
;
Mice
;
Microscopy, Electron
;
Neurons/metabolism/ultrastructure
;
Tay-Sachs Disease/*drug therapy/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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