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

Mina, J.G.; Denny, P.W.

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


Authors



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.

Citation

Mina, J., & Denny, P. (2018). Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis. Parasitology, 145(2), 134-147. https://doi.org/10.1017/s0031182017001081

Journal Article Type Article
Acceptance Date May 28, 2017
Online Publication Date Jun 22, 2017
Publication Date Feb 1, 2018
Deposit Date May 15, 2017
Publicly Available Date Mar 29, 2024
Journal Parasitology
Print ISSN 0031-1820
Electronic ISSN 1469-8161
Publisher Cambridge University Press
Peer Reviewed Peer Reviewed
Volume 145
Issue 2
Pages 134-147
DOI https://doi.org/10.1017/s0031182017001081

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Advance online version © Cambridge University Press 2017. This is an Open Access article, distributed under the terms of the
Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution,
and reproduction in any medium, provided the original work is properly cited.






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