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An overview of the fatty acid biosynthesis in the protozoan parasite Leishmania and its relevance as a drug target against leishmaniasis

Journal

MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 246, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.molbiopara.2021.111416

Keywords

Leishmania; Trypanosoma; Drugs; Lipids and fatty acid biosynthesis; Phosphopantetheinyl transferase or PPT; Elongases

Funding

  1. University Grants Commission
  2. Lady Tata Memorial Trust, India
  3. Institution of Eminence, University of Delhi
  4. University of Delhi (R&D grant), Department of Science and Technology (PURSE grant)
  5. UGC SAP programme, Government of India
  6. National Institute of Immunology, India
  7. UGC-DAE CSR, Indore, India [CSR-IC-BL-01/CRS-98-2019-20/198]

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Leishmaniasis is a fast-growing parasitic disease worldwide, with the fatty acid biosynthetic pathway identified as a potential drug target against parasite infections. Understanding the mechanisms of fatty acid metabolism in parasites is crucial for developing new therapeutics, but further research in this direction is needed.
Leishmaniasis is one of the fast-growing parasitic diseases worldwide. The treatment of this fatal disease presents a daunting challenge because of its adverse effects, necessity for long-term treatment regime, unavailability of functional drugs, emergence of drug resistance and the related expenditure. This calls for an urgent need for novel drugs and the evaluation of new targets. Proteins of the fatty acid biosynthetic pathway are validated as drug targets in pathogenic bacteria and certain viruses. Likewise, this pathway has been speculated as a suitable target against parasite infections. Fatty acid synthesis in parasites seems to be very complex and distinct from the counterpart mammalian host due to the presence of unique mechanisms for fatty acid biosynthesis and acquisition. In recent times, there have been few evidences of the existence of this pathway in the bloodstream form of some pathogens. The fatty acid biosynthesis thus presents a viable and attractive target for emerging therapeutics. Understanding the mechanisms underlying fatty acid metabolism is key to identifying a potential drug target. However, investigations in this direction are still limited and this article attempts to outline the existing knowledge, while highlighting the scope and relevance of the fatty acid biosynthetic pathway as a drug target. This review highlights the advances in the treatment of leishmaniasis, the importance of lipids in the pathogen, known facts about the fatty acid biosynthesis in Leishmania and how this pathway can be manipulated to combat leishmaniasis, suggesting novel drug targets.

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