The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

Michael A. J. Ferguson, John S. Brimacombe, Jillian R. Brown, Arthur Crossman, Alexander Dix, Robert A. Field, M. Lucia S. Guther, Kenneth G. Milne, Deepak K. Sharma, Terry K. Smith

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    117 Citations (Scopus)

    Abstract

    African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)327-340
    Number of pages14
    JournalBiochimica et Biophysica Acta. Molecular Basis of Disease
    Volume1455
    Issue number2-3
    DOIs
    Publication statusPublished - 1999

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