The blood-brain barrier and treatment of lysosomal storage diseases

Lysosomes are ubiquitous, acidic intracellular compartments that fulfil a crucial role in degradation of macromolecules in cells. Specific lysosomal catabolic reactions may be impaired due to inherited defects in specific hydrolases, resulting in gradual intralysosomal accumulation of corresponding endogenous substrates. Such lysosomal deficiencies may ultimately result in devastating clinical symptoms, the so-called lysosomal storage diseases. Many of the inherited lysosomal storage disorders show phenotypic variants in which neurological complications are prominent as the result of pathological storage formation in cells inside the brain, for example perivascular macrophages, microglia or neuronal cells. In this chapter new developments and present limitations regarding therapy of (neuronopathic) lysosomal storage diseases are reviewed.