Receptor-mediated endocytosis of α-galactosidase a in human podocytes in Fabry disease

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Abstract

Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs. © 2011 Prabakaran et al.

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Prabakaran, T., Nielsen, R., Larsen, J. V., Sørensen, S. S., Feldt-Rasmussen, U., Saleem, M. A., … Christensen, E. I. (2011). Receptor-mediated endocytosis of α-galactosidase a in human podocytes in Fabry disease. PLoS ONE, 6(9). https://doi.org/10.1371/journal.pone.0025065

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