Preclinical research of a new therapy for Gaucher's disease with F213I mutation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To design and make trial of a new therapy for Gaucher disease.</p><p><b>METHODS</b>A substrate analogue of beta-Glc (glucocerebroside analogue, GCA) was used as a molecular chaperon. Normal and mutant skin fibroblasts were cultured with or without GCA. The activity of beta-Glc was assayed by fluorescent enzymologic techniques. The amount of beta-Glc was determined using Western blot. The beta -Glc was localized by double cell stain experiment. The degradation of glucocerebroside was assessed by thin layer chromatography (TLC) experiment using 14C-Serine.</p><p><b>RESULTS</b>It was found that GCA could enhance the activity and amount of beta-Glc with F213I mutation. It also promoted the beta-Glc with F213I mutation to the lysosome and accelerated the degradation of glucocerebroside.</p><p><b>CONCLUSION</b>The low molecular compound analogous to beta-Glc substrate (GCA ) may be a new therapeutic strategy for Gaucher's disease with F213I mutation.</p>

Studies on the molecular mechanism of GM(2) gangliosidosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the molecular mechanism of GM(2) gangliosidosis.</p><p><b>METHODS</b>The skin fibroblasts from 4 patients with GM(2) gangliosidosis were subjected to culture. Enzyme activities assay, Western blot and immunocytochemical analysis were performed using the cultured fibroblasts.</p><p><b>RESULTS</b>The hexosaminidase (Hex) activities of 4 patients with GM(2) gangliosidosis were significantly decreased. The activities were 12% 3% 15% and 6% of control values, respectively. Western blot analysis indicated that the amount of Hex mature alpha- and beta- subunits (alpha m, beta m) was decreased in cells from patients 2 and 3, but only decreased alpha m was found in patient 1 and both alpha m and beta m were normal in cells from patient 4. Immunocytochemical analysis revealed the accumulated GM(2) ganglioside in cells from patients 1-4.</p><p><b>CONCLUSION</b>The pathogenesis of GM(2) gangliosidosis was associated with deficiency of Hex alpha m and beta m and GM(2) activator caused by HEXA, HEXB and GM(2)A gene mutations.</p>