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: F M Platt, G R Neises, G Reinkensmeier, M J Townsend, V H Perry, R L Proia, B Winchester, R A Dwek, T D Butters
• Journal: Science (New York, N.Y.) (Science) Vol. 276 Issue 5311 Pg. 428-31 (Apr 18 1997) ISSN: 0036-8075 [Print] United States
• PMID: 9103204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• 1-Deoxynojirimycin
• G(M2) Ganglioside
• miglustat

Topics

• 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)