Lysosomal storage disorders.
Although the first description of a lysosomal storage disorder was that of Tay-Sachs disease in 1881, the lysosome was not discovered until 1955, by Christian De Duve. The first demonstration by Hers in 1963 of a link between an enzyme deficiency and a storage disorder (Pompe's disease) paved the way for a series of seminal discoveries about the intracellular biology of these enzymes and their substrates, culminating in the successful treatment of Gaucher's disease with beta-glucosidase in the early 1990s. It is now recognized that these disorders are not simply a consequence of pure storage, but result from perturbation of complex cell signalling mechanisms. These in turn give rise to secondary structural and biochemical changes, which have important implications for therapy. Significant challenges remain, particularly the treatment of central nervous system disease. It is hoped that recent advances in our understanding of lysosomal biology will enable successful therapies to be developed.
Vellodi
Ashok
A
Metabolic Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK. velloa@gosh.nhs.uk.
D006801:Humans; D016464:Lysosomal Storage Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008247:Lysosomes / Q000201:enzymology / Q000502:physiology; D017628:Microglia / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology