Abstract Sandhoff disease (SD) is an ultra-rare lysosomal storage disorder (LSD), which affects ~ 1/1000, 000 live birth. SD caused by genetic deficiency of beta (β) Hexosaminidase and resulting excess central nervous system (CNS) synthesis GM2 ganglioside (GM2) its impact on neuron death. The exact mechanisms underlying such GM2-driven death are unknown in SD. Glucosylceramide (GC) induced com...

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...

The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosami...

Sandhoff disease is a recessively inherited lysosomal storage disease resulting from a deficiency of beta-hexosaminidase activity. The enzyme occurs in two major forms, beta-hexosaminidase A, composed of an alpha- and beta-subunit and beta-hexosaminidase B, composed of two beta-subunits. Both isozyme activities are deficient in Sandhoff disease, owing to mutations of the HEXB gene encoding the ...

TAKEDA, K., NAKAI, H., HAGIWARA, H., TADA, K., SHOWS, T.S., BYERS, MG. and MYEROWITZ, R. Fine Assignment of R-Hexosaminidase A a-Subunit on 15g23-q24 by High Resolution In Situ Hybridization. Tohoku J. Exp. Med., 1990, 160 (3), 203-211 Tay-Sacks disease results from mutation in the gene encoding /3-hexosaminidase A a-Subunit. Although some reports have suggested the locus on 15q, we tried to de...

Egress of free NeuAc from normal lysosome-rich granular fractions was assessed at NeuAc concentrations of up to 221 pmol/hexosaminidase unit, achieved by exposure of growing fibroblasts to 40-125 nM N-acetylmannosamine for up to 7 days. The normal velocity of NeuAc egress increased with NeuAc loading and with temperature, exhibiting a Q10 of 2.4, characteristic of carrier-mediated transport. Fi...

A novel monosialoganglioside was isolated from Tay-Sachs brains. It represented about 0.1% of the total ganglioside mixture. Compositional analysis by gas-liquid chromatography indicated that it contained glucose, galactose, N-acetylgalactosamine, N-acetylneuraminic acid, and long chain base in the molar ratio of 1:2:2:1:1. The ganglioside was found to be resistant to neuraminidase (Clostridium...

The lysosomal enzyme, @-hexosaminidase, is composed of two chains, a and 8. In Tay-Sachs disease, mutations in the gene encoding the a-chain produce a @-hexosaminidase deficiency that results in the storage of its natural substrate, GMz ganglioside. To obtain the background information for the eventual identification of the mutational errors in Tay-Sachs disease and to determine possible relati...

Sandhoff Disease (SD) is an autosomal recessive neurodegenerative disease caused by a mutation in the Hexb gene for the β-subunit of β-hexosaminidase A, resulting in the inability to catabolize ganglioside GM2 within the lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2 primarily in the CNS. Myelin-enriched glycolipids, cerebrosides and sulfatides, are also decrea...

background: glycosidases profusion in male reproductive fluids suggests a possible relationship with sperm function. although hexosaminidase (hex) is the most active glycosidase in epididymal fluid and seminal plasma, as well as in spermatozoa, glucosidase is considered a marker for epididymal function and azoospermia. objective: the aim of this study was to determine hex activity in seminal pl...