Sialidase-mediated depletion of GM2 ganglioside in Tay-Sachs neuroglia cells.
Tay-Sachs disease is a severe, inherited disease of the nervous system caused by accumulation of the brain lipid GM2 ganglioside. Mouse models of Tay-Sachs disease have revealed a metabolic bypass of the genetic defect based on the more potent activity of the enzyme sialidase towards GM2. To determine whether increasing the level of sialidase would produce a similar effect in human Tay-Sachs cells, we introduced a human sialidase cDNA into neuroglia cells derived from a Tay-Sachs fetus and demonstrated a dramatic reduction in the accumulated GM2. This outcome confirmed the reversibility of GM2 accumulation and opens the way to pharmacological induction or activation of sialidase for the treatment of human Tay-Sachs disease.
Igdoura
S A
SA
Montreal Children's Hospital Research Institute and Department of Human Genetics, McGill University, Quebec, Canada.
Mertineit
C
C
Trasler
J M
JM
Gravel
R A
RA
D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005678:G(M2) Ganglioside / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000201:enzymology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014162:Transfection
D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D005678:G(M2) Ganglioside; D009439:Neuraminidase