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

ABSTRACT

<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>