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Galactonojirimycin derivatives restore mutant human beta-galactosidase activities expressed in fibroblasts from enzyme-deficient knockout mouse.
- Source :
-
Brain & development [Brain Dev] 2001 Aug; Vol. 23 (5), pp. 284-7. - Publication Year :
- 2001
-
Abstract
- Ten low molecular compounds analogous to galactose were screened for inhibition of human beta-galactosidase activity. Among them, 1-deoxy-galactonojirimycin and N-(n-butyl)-deoxy-galactonojirimycin showed an inhibitory effect at high concentrations. However, they restored mutant enzyme activities expressed in enzyme-deficient knockout mouse fibroblasts and human beta-galactosidosis fibroblasts at lower intracellular concentrations. This effect was more remarkable on G(M1)-gangliosidosis mutations (R201C, I51T, R201H, R457Q) than Morquio B disease mutations (W273L, Y83H). These low molecular compounds pass though the blood-brain barrier in mice. We hope that this new therapeutic approach will become clinically applicable in the near future.
- Subjects :
- 1-Deoxynojirimycin analogs & derivatives
Animals
Cells, Cultured cytology
Cells, Cultured enzymology
DNA, Complementary drug effects
DNA, Complementary pharmacology
Fibroblasts cytology
Fibroblasts enzymology
Gangliosidosis, GM1 enzymology
Gangliosidosis, GM1 physiopathology
Humans
Mice
Mice, Knockout genetics
Mice, Knockout metabolism
Mucopolysaccharidosis IV enzymology
Mucopolysaccharidosis IV physiopathology
Mutation drug effects
Mutation physiology
beta-Galactosidase deficiency
beta-Galactosidase genetics
1-Deoxynojirimycin pharmacology
Cells, Cultured drug effects
Fibroblasts drug effects
Gangliosidosis, GM1 drug therapy
Mucopolysaccharidosis IV drug therapy
beta-Galactosidase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0387-7604
- Volume :
- 23
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Brain & development
- Publication Type :
- Academic Journal
- Accession number :
- 11504597
- Full Text :
- https://doi.org/10.1016/s0387-7604(01)00216-9