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Glycosphingolipids and Kidney Disease

  • Chapter
Sphingolipids and Metabolic Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 721))

Abstract

Glycosphingolipids, derived from the addition of sugar-moieties to the sphingolipid ceramide, are highly abundant in the kidney. Glycosphingolipids are known to play an important role in organ function at least in part from inherited lipid storage diseases such as Anderson-Fabry disease (Fabry’s disease; FD) that results from a mutation in alpha-galactosidase a (α-GLA or α-Gal A), the enzyme responsible for catalyzing the removal of terminal galactose residues from glycosphingolipids. The inactivation in α-GLA in FD results in the accumulation of glycosphingolipids, including globosides and lactosylceramides, which manifests as several common pathologies including end-stage kidney disease. More recently, glycosphingolipids and other sphingolipids have become increasingly recognized for their roles in a variety of other kidney diseases including polycystic kidney disease, acute kidney injury, glomerulonephritis, diabetic nephropathy and kidney cancer. This chapter reviews evidence supporting a mechanistic role for glycosphingolipids in kidney disease and discusses data implicating a role for these lipids in kidney disease resulting from metabolic syndrome. Importantly, inhibitors of glycosphingolipid synthesis are well tolerated in animal models as well as in humans. Thus, an increased understanding of the mechanisms by which altered renal glycosphingolipid metabolism leads to kidney disease has great therapeutic potential.

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  1. Department of Medicine, Division of General Internal Medicine/Geriatrics, Medical University of South Carolina, Charleston, South Carolina, USA

    Andrew R. Mather & Leah J. Siskind

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    L. Ashley Cowart PhD

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Mather, A.R., Siskind, L.J. (2011). Glycosphingolipids and Kidney Disease. In: Cowart, L.A. (eds) Sphingolipids and Metabolic Disease. Advances in Experimental Medicine and Biology, vol 721. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0650-1_8

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