Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis

John G. M. Mina, P. W. Denny

    Research output: Contribution to journalConference article

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    Abstract

    Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites. In this review we focus on the key enzymes of the SL de novo biosynthetic pathway in protozoan parasites of the Apicomplexa and Kinetoplastidae, outlining the divergence and interconnection between host and pathogen metabolism. The druggability of the SL biosynthesis is considered, alongside recent technology advances that will enable the dissection and analyses of this pathway in the parasitic protozoa. The future impact of these advances for the development of new therapeutics for both globally threatening and neglected infectious diseases is potentially profound.
    Original languageEnglish
    Pages (from-to)134-147
    Number of pages14
    JournalParasitology
    Volume145
    Issue numberSpecial Issue 2
    Early online date22 Jun 2017
    DOIs
    Publication statusPublished - 28 Feb 2018
    EventBritish Society for Parasitology: Autumn Symposium on Microbial Protein Targets - Towards Understanding and Intervention - Durham University, Durham, United Kingdom
    Duration: 14 Sep 201616 Sep 2016

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