New beta-galactosidase activity detected in cell extracts of phage DNA-treated GMI-gangliosidosis fibroblasts continued to vary considerably from one experiment to another.
Two variants of type-ABGM2-gangliosidosis can be distinguished by using p-nitrophenyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside (PNP-GlcNAc-6-SO4) as substrate.
We identified a 1422 G-->C (amino acid W474C) substitution in the first position of exon 13 of HEXA of a non-Jewish proband who manifested a subacute variant of G(M2) gangliosidosis.
W474C amino acid substitution affects early processing of the alpha-subunit of beta-hexosaminidase A and is associated with subacute G(M2) gangliosidosis.
In addition to accumulating cholesterol, NPC1-deficient cells also accumulate gangliosides and other glycosphingolipids (GSLs), and neuropathological abnormalities in NPC disease closely resemble those seen in primary gangliosidoses.
In line with reports by Reymond and Jäger on similar structures, these amine containing basic carbasugars are potent inhibitors of β-D-galactosidases and, for the first time, could be shown to act as pharmacological chaperones for G<sub>M1</sub>-gangliosidosis-associated lysosomal acid β-galactosidase mutant R201C, thus representing a new structural type of pharmacological chaperones for this lysosomal storage disease.
A new type of pharmacological chaperone for G<sub>M1</sub>-gangliosidosis related human lysosomal β-galactosidase: N-Substituted 5-amino-1-hydroxymethyl-cyclopentanetriols.