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

M A J Ferguson, J S Brimacombe, J R Brown, A Crossman, A Dix, R A Field, M L S Guther, K G Milne, D K Sharma, T K Smith

Research output: Contribution to journalReview articlepeer-review

120 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 - 8 Oct 1999

Keywords

  • glycosylphosphatidylinositol
  • GPI
  • trypanosome
  • biosynthesis
  • glycosyltransferase
  • VARIANT SURFACE GLYCOPROTEIN
  • GLYCOSYLPHOSPHATIDYLINOSITOL MEMBRANE ANCHOR
  • GLYCOSYL-PHOSPHATIDYLINOSITOL ANCHOR
  • GLYCOINOSITOL PHOSPHOLIPID ANCHOR
  • N-ACETYLGLUCOSAMINYL-PHOSPHATIDYLINOSITOL
  • HUMAN-ERYTHROCYTE ACETYLCHOLINESTERASE
  • ASPARAGINE-LINKED OLIGOSACCHARIDES
  • TRYPANOSOMA-CRUZI 1G7-ANTIGEN
  • MOLECULAR-SPECIES ANALYSIS
  • SACCHAROMYCES-CEREVISIAE

Fingerprint

Dive into the research topics of 'The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness'. Together they form a unique fingerprint.

Cite this