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Glycobiology, 2000, Vol. 10, No. 12 1249-1258
© 2000 Oxford University Press

MINI REVIEW

Stemming the tide: glycosphingolipid synthesis inhibitors as therapy for storage diseases

Cynthia J. Tifft2 and Richard L. Proia1

Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA, and 2Department of Medical Genetics, Children’s National Medical Center, Washington, DC 20010, USA

Abstract

Glycosphingolipids (GSLs) are plasma membrane components of every eukaryotic cell. They are composed of a hydrophobic ceramide moiety linked to a glycan chain of variable length and structure. Once thought to be relatively inert, GSLs have now been implicated in a variety of biological processes. Recent studies of animals rendered genetically deficient in various classes of GSLs have demonstrated that these molecules are important for embryonic differentiation and development as well as central nervous system function. A family of extremely severe diseases is caused by inherited defects in the lysosomal degradation pathway of GSLs. In many of these disorders GSLs accumulate in cells, particularly neurons, causing neurodegeneration and a shortened life span. No effective treatment exists for most of these diseases and little is understood about the mechanisms of pathogenesis. This review will discuss the development of a new approach to the treatment of GSL storage disorders that targets the major synthesis pathway of GSLs to stem their cellular accumulation.

Footnotes

1 To whom correspondence should be addressed at: National Institutes of Health, Building 10, Room 9N314, Bethesda, MD 20892. Copyright does not extend to this article, which is a work of the United States government.


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