Pathology and Current Treatment of Neurodegenerative Sphingolipidoses

摘要: Sphingolipidoses constitute a large subgroup of lysosomal storage disorders (LSDs). Many them are associated with progressive neurodegeneration. As is the case for LSDs in general, most sphingolipidoses caused by deficiencies hydrolases. However, accumulation sphingolipids can also result from proteins involved transport or posttranslational modification enzymes, lipids, membrane required degradation end products. The lysosome together secondary changes concentration and localization other lipids may cause trafficking defects proteins, affect calcium homeostasis, induce unfolded protein response, activate apoptotic cascades, various signal transduction pathways. To what extent, however, these contribute to pathogenesis diseases not fully understood. Currently, there no cure sphingolipidoses. Therapies like enzyme replacement, pharmacological chaperone, substrate reduction therapy, which have been shown be efficient non-neuronopathic LSDs, currently evaluated clinical trials neuronopathic In future, neural stem cell therapy gene become an option disorders.