Biology and potential strategies for the treatment of GM2 gangliosidoses.
The GM2 gangliosidoses are a group of heritable neurodegenerative disorders caused by excessive accumulation of the ganglioside GM2 owing to deficiency in beta-hexosaminidase activity. Tay-Sachs and Sandhoff diseases have similar clinical phenotypes resulting from a deficiency in human hexosaminidase alpha and beta subunits, respectively. The lack of treatment for GM2 gangliosidoses stimulated interest in developing animal models to understand the molecular mechanisms underlying the various forms of this disease and to test new potential therapies. In this review, we discuss the molecular biology of GM2 gangliosidoses and the different strategies that have been tested in animal models for the treatment of this genetic disorder, including gene transfer and cell engraftment of neural stem cells engineered to express the hexosaminidase isoenzymes.
Chavany
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C
Genetics and Molecular Immunology Section, National Institutes of Health, Bethesda, MD 20892, USA.
Jendoubi
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M
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation; D002415:Cats; D017690:Cell Transplantation; D002648:Child; D004195:Disease Models, Animal; D004285:Dogs; D005678:G(M2) Ganglioside / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006017:Glycolipids / Q000378:metabolism; D006678:HIV / Q000235:genetics; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000637:transplantation; D010641:Phenotype; D017354:Point Mutation; D051381:Rats; D012497:Sandhoff Disease / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D013552:Swine; D013661:Tay-Sachs Disease / Q000208:ethnology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D014184:Transplantation, Homologous; D001619:beta-N-Acetylhexosaminidases / Q000008:administration & dosage / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use
D006017:Glycolipids; D017485:1-Deoxynojirimycin; D005678:G(M2) Ganglioside; C059896:miglustat; D001619:beta-N-Acetylhexosaminidases