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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sphingolipids
Sphingolipids
new drugs
Protozoa
biosynthesis
Pharmaceutical Preparations
Parasites
Neglected Diseases
Apicomplexa
parasites
Biosynthetic Pathways
infectious diseases
Communicable Diseases
biochemical pathways
Dissection
Technology
therapeutics
metabolism
synthesis
Membranes

Cite this

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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.",
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Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis. / Mina, John G. M.; Denny, P. W.

In: Parasitology, Vol. 145, No. Special Issue 2, 28.02.2018, p. 134-147.

Research output: Contribution to journalConference article

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AB - 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.

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