Differential Accumulation of Glycosphingolipids in a Tay-Sachs Disease Brain

摘要

Tay-Sachs disease (TSD) is a fatal disease of massive accumulation of GM2 ganglioside in the brain due to the deficiency of b-hexosaminidase A (Hex A) or GM2 activator protein. Clinically, TSD includes three different phenotypes: the acute infantile form, the late-onset juvenile form, and the adult form. The heterogeneity of TSD is poorly understood and cannot be attributed to any specific gene mutation. We seek to address the question of how the accumulation of GM2 (and possibly other glycosphingolipids) leads to different disease phenotypes and tissue dysfunction.