Prevention of lysosomal storage in Tay-Sachs mice treated with N- butyldeoxynojirimycin
Prevention of lysosomal storage in Tay-Sachs mice treated with N- butyldeoxynojirimycin
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 G(M2) 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 (G(M2)) for the defective enzyme (β-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.
428-431
Platt, Frances M.
3b0d9f95-fba8-4083-91e2-c567c3e77582
Neises, Gabrielle R.
37f78118-81fd-4577-b63a-d6403899e9f6
Reinkensmeier, Gabriele
511115ff-208d-45fd-802c-4e2514f1f9bb
Townsend, Mandy J.
2c631395-a90e-4f3b-aa54-2712a1807faa
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Proia, Richard L.
c1c20347-9813-462b-8fe2-111b430c429a
Winchester, Bryan
03541c2c-7a1d-4364-ae07-de2762a31088
Dwek, Raymond A.
5fb1a0ce-1ac6-4825-8ff0-f62c7164ff0c
Butters, Terry D.
891552e5-fab9-49f8-9e0a-7fccb5920e35
18 April 1997
Platt, Frances M.
3b0d9f95-fba8-4083-91e2-c567c3e77582
Neises, Gabrielle R.
37f78118-81fd-4577-b63a-d6403899e9f6
Reinkensmeier, Gabriele
511115ff-208d-45fd-802c-4e2514f1f9bb
Townsend, Mandy J.
2c631395-a90e-4f3b-aa54-2712a1807faa
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Proia, Richard L.
c1c20347-9813-462b-8fe2-111b430c429a
Winchester, Bryan
03541c2c-7a1d-4364-ae07-de2762a31088
Dwek, Raymond A.
5fb1a0ce-1ac6-4825-8ff0-f62c7164ff0c
Butters, Terry D.
891552e5-fab9-49f8-9e0a-7fccb5920e35
Platt, Frances M., Neises, Gabrielle R. and Reinkensmeier, Gabriele
,
et al.
(1997)
Prevention of lysosomal storage in Tay-Sachs mice treated with N- butyldeoxynojirimycin.
Science, 276 (5311), .
(doi:10.1126/science.276.5311.428).
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 G(M2) 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 (G(M2)) for the defective enzyme (β-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.
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Published date: 18 April 1997
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Local EPrints ID: 489608
URI: http://eprints.soton.ac.uk/id/eprint/489608
ISSN: 0036-8075
PURE UUID: a573ddc0-2a59-44c9-aebf-7b5ce5281149
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Date deposited: 29 Apr 2024 16:46
Last modified: 29 Apr 2024 16:46
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Author:
Frances M. Platt
Author:
Gabrielle R. Neises
Author:
Gabriele Reinkensmeier
Author:
Mandy J. Townsend
Author:
Richard L. Proia
Author:
Bryan Winchester
Author:
Raymond A. Dwek
Author:
Terry D. Butters
Corporate Author: et al.
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