Therapeutic strategies to ameliorate lysosomal storage disorders - a focus on Gaucher disease.

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Ghislaine SURREL

maladies-lysosomales-subscribe@yahoogroupes.fr

Cell Mol Life Sci. 2006 Mar 29; [Epub ahead of print]
Sawkar AR, D'Haeze W, Kelly JW.

Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA, jkelly@scripps.edu.

The lysosomal storage disorders encompass more than 40 distinct diseases, most of which are caused by the deficient activity of a lysosomal hydrolase leading to the progressive, intralysosomal accumulation of substrates such as sphingolipids, mucopolysaccharides, and oligosaccharides. Here, we primarily focus on Gaucher disease, one of the most prevalent lysosomal storage disorders, which is caused by an impaired activity of glucocerebrosidase, resulting in the accumulation of the glycosphingolipid glucosylceramide in the lysosomes. Enzyme replacement and substrate reduction therapies have proven effective for Gaucher disease cases without central nervous system involvement. We discuss the promise of chemical chaperone therapy to complement established therapeutic strategies for Gaucher disease. Chemical chaperones are small molecules that bind to the active site of glucocerebrosidase variants stabilizing their threedimensional structure in the endoplasmic reticulum, likely preventing their endoplasmic reticulum-associated degradation and allowing their proper trafficking to the lysosome where they can degrade accumulated substrate to effectively ameliorate Gaucher disease.

PMID: 16568247 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16568247&query_hl=1&itool=pubmed_docsum

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