title: Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin.
abstract: 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.
authors.affiliation: Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford 0X1 3QU, UK. fran@oxglua.glycob.ox.ac.uk
authors.forename: F M
authors.initials: FM
authors.lastname: Platt
authors.forename: G R
authors.initials: GR
authors.lastname: Neises
authors.forename: G
authors.initials: G
authors.lastname: Reinkensmeier
authors.forename: M J
authors.initials: MJ
authors.lastname: Townsend
authors.forename: V H
authors.initials: VH
authors.lastname: Perry
authors.forename: R L
authors.initials: RL
authors.lastname: Proia
authors.forename: B
authors.initials: B
authors.lastname: Winchester
authors.forename: R A
authors.initials: RA
authors.lastname: Dwek
authors.forename: T D
authors.initials: TD
authors.lastname: Butters
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005678:G(M2) Ganglioside / Q000096:biosynthesis / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D013661:Tay-Sachs Disease / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; D005678:G(M2) Ganglioside; C059896:miglustat