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

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

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: Jun 28, 2017
• 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
• Public URL: https://durham-repository.worktribe.com/output/1358368