Sandhoff disease, a GM2 gangliosidosis caused by a deficiency in β-hexosaminidase, is characterized by progressive neurodegeneration. Although loss of neurons in association with lysosomal storage of glycosphingolipids occurs in patients with this disease, the molecular pathways that lead to the accompanying neurological defects are unclear. Using an authentic murine model of GM2 gangliosidosis...

Niemann-Pick type C (NPC)1 is a rare neurodegenerative disease for which treatment options are limited. A major barrier to development of effective treatments has been the lack of validated biomarkers to monitor disease progression or serve as outcome measures in clinical trials. Using targeted metabolomics to exploit the complex lipid storage phenotype that is the hallmark of NPC1 disease, we ...

GD3, a ganglioside expressed on human melanoma, can be recognized by the humoral immune system. In this paper, we demonstrate that immunizing mice with the human melanoma cell line SK-MEL-28 (GD3+ GM2- CD1-) or with syngeneic APCs loaded with GD3 can induce a GD3-reactive natural killer T (NKT) cell response. GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencie...

BACKGROUND Sandhoff disease is an autosomal recessive disorder caused by β-hexosaminidase deficiency and accumulation of GM2 ganglioside resulting in progressive motor neuron manifestations and death from respiratory failure and infections in infantiles. Pathogenic mutations in HEXB gene were observed which leads to enzyme activity reduction and interruption of normal metabolic cycle of GM2 gan...

In order to elucidate some of the factors that determine the characteristic expression of gangliosides in malignant melanoma and neuroblastoma the levels of ganglioside synthases (glycosyltransferases) were determined in a panel of cell lines from those tumors that exhibited a wide range of ganglioside composition. Sialyltransferases (GM3, GD3, GD1a, and GT1b synthases), N-acetylgalactosaminylt...

Tay-Sachs disease (TSD) is a lysosomal storage disease that is inherited in an autosomal recessive pattern. Lysosomal storage diseases are a group of disorders characterized by deficiency of a specific single lysosomal enzyme, resulting in accumulation of abnormal metabolic products. TSD is characterized by a deficiency in a common lysosomal acid hydrolase, hexosaminidase A (Hex A). An insuffic...

To establish a model system for the study of ganglioside metabolism of the human brain tumor, medulloblastoma, we have chemically characterized the gangliosides of the Daoy cell line. These cells contain a high concentration of gangliosides (143 +/- 13 nmol LBSA/10(8) cells). The major species have been structurally confirmed to be GM2 (65.9%), GM3 (13.0%), and GD1a (10.3%). Isolation of indivi...

BACKGROUND Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. METHODS In this study, we examined 31 patients for TSD-causing mu...

Using beta 1,4-N-acetylgalactosaminyltransferase (EC 2.4.1.92) complementary DNA, the correlation of gene expression, enzyme activity, and expression of ganglioside antigens was analyzed in 20 human tumor cell lines. In many lines, GM2 and/or GD2 were the most complex structures examined. Northern blot analysis revealed 5.2- and 3.0-kilobase mRNAs in almost all cell lines expressing GD2 and/or ...