Induced secretion of beta-hexosaminidase by human brain endothelial cells: a novel approach in Sandhoff disease?
Neurobiol Dis
; 37(3): 656-60, 2010 Mar.
Article
em En
| MEDLINE
| ID: mdl-20005954
ABSTRACT
Sandhoff disease is an autosomal recessive lysosomal disorder due to mutations in the beta-hexosaminidase beta-chain gene, resulting in beta-hexosaminidases A (alphabeta) and B (betabeta) deficiency and GM2 ganglioside accumulation in the brain. In this study, our aim was to demonstrate that transduction of cerebral endothelial cells cultured in two-chamber culture inserts with a lentiviral vector encoding the hexosaminidases alpha and beta chains could induce a vectorial secretion of hexosaminidases. Therefore, the human cerebral endothelial cell line hCMEC/D3 was infected with the bicistronic vector from the apical compartment, and beta-hexosaminidase activity was measured in transduced cells and in deficient fibroblasts co-cultured in the basal (i.e. brain) compartment. Induced beta-hexosaminidase secretion by transduced hCMEC/D3 cells was sufficient to allow for a 70-90% restoration of beta-hexosaminidase activity in deficient fibroblasts. On the basis of these in vitro data, we propose that brain endothelium be considered as a novel therapeutic target in Sandhoff disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Sandhoff
/
Transdução Genética
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Beta-N-Acetil-Hexosaminidases
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Terapia Genética
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Células Endoteliais
Limite:
Humans
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França