Therapy of Lysosomal Storage Diseases

摘要: Lysosomes are membrane-surrounded organelles which present in all nucleated mammalian cells. They function to degrade both intra- and extracellular macromolecules low molecular components that transported the cytoplasm for reutilization biosynthetic pathways of cell. Up now more than 50 different lysosomal hydrolases catalyzing degradation proteins, lipids, nucleic acids carbohydrates have been identified. The normal compartment also depends on a variety proteins without hydrolytic activity such as cofactors, transporters, ion channels nonlysosomal engaged posttranslational activation targeting enzymes. Functional deficiencies, or nonhydrolytic polypeptides can result storage diseases (LSDs) characterized by intralysosomal deposition multisystemic phenotype leading early death. Most LSDs appear severe, onset forms milder, late variants. This hetereogeneity seems be due subtle differences residual amount active protein implying even modest increase level might beneficial effects disease. Consequently, most therapies attempt supply deficient cells with counterpart defective protein. Such enzyme augmentation contrast substrate reduction try reduce accumulated material nonenzymatic means. evaluation potentials, limitations risks therapeutic strategies cell culture animal models has fundamental implementation clinical trials finally led realization certain treatment concepts.