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...

Sujiaonori, a river alga growing in the Kochi prefecture, Japan, contains several bioactive compounds such as sulfated polysaccharides (ulvans), ω-3 fatty acids, and vitamins. Dietary intake of this alga-based supplement has been reported to increase circulatory adiponectin, a salutary hormone that is reported to be associated with healthy longevity and prevents a number of cardiovascular and m...

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...

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...