Prevention of Lysosomal Storage in Tay-Sachs Mice Treated with N-Butyldeoxynojirimycin
FM Platt, GR Neises, G Reinkensmeier, MJ Townsend… - Science, 1997 - science.org
Science, 1997•science.org
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 GM2in the brain was prevented, with the number of storage neurons and the quantity 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 GM2in the brain was prevented, with the number of storage neurons and the quantity of …
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 biosynthesisN-butyldeoxynojirimycin, was evaluated in a mouse model of Tay-Sachs disease. When Tay-Sachs mice were treated withN-butyldeoxynojirimycin, the accumulation of GM2in 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 (β-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.
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