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SYSTEMATIC REVIEW article

Front. Med.
Sec. Infectious Diseases: Pathogenesis and Therapy
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1441352
This article is part of the Research Topic New Perspectives on Antimalarial Drug Development and Drug Resistance View all 3 articles

Ubiquitin-Proteasome System in Plasmodium: a potential antimalarial target to overcome resistance -a systematic review

Provisionally accepted
Adriana F. Gonçalves Adriana F. Gonçalves 1,2*Ana Lima-Pinheiro Ana Lima-Pinheiro 1,2Pedro E. Ferreira Pedro E. Ferreira 1,2*
  • 1 Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal
  • 2 ICVS/3B’s Associate Laboratory, Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimaraes, Braga, Portugal

The final, formatted version of the article will be published soon.

    Background: Malaria is a devasting parasitic disease that causes over half a million deaths every year. The necessity for prompt and thorough antimalarial drug discovery and development is accelerated by the rise in multidrug resistance and the lack of an effective vaccine. The Plasmodium spp. proteasome represents a prospective target for antimalarial treatment since several chemotherapy types have been shown to potently and selectively limit the growth of parasites. Combined with first-line artemisinin medicines, it creates synergy, even in the artemisinin-resistant parasites.Methods: PRISMA guidelines were used in the development of this systematic review. A literature search was performed in March 2024 in PubMed, Science Direct, and Scopus databases, with the following keywords: ((antimalarial resistance) AND (plasmodium OR malaria) AND (proteasome)) NOT (cancer [Title/Abstract]). Only articles with the susceptibility assessment were included.Results: Herein, 35 articles were included in the systematic review, which was divided into two subcategories: those that studied the UPS inhibitors, which accounted for 25 articles, and those that studied genetic modifications, including knockouts, knockdowns, and mutations, in the UPS towards antimalarial resistance, accounting for 16 articles. 6 articles included both subcategories. In total, 16 categories of inhibitors were analyzed, together with two knockdowns, one knockout, and 35 mutations.In this study, we reviewed the literature for available inhibitors and their respective susceptibility and ability to develop resistance toward Plasmodium spp. 26s proteasome. The proteasome was highlighted as a potential antimalarial target and as an artemisinin partner drug. However, host toxicity and susceptibility to resistance appear as the main obstacle in the development of highly potent drugs, indicating a need for additional scrutiny during any further drug development efforts.

    Keywords: antimalarial resistance, Artemisinin, Ubiquitin-proteasome system (UPS), Plasmodium spp., Proteasome Inhibitors Proteasome in Plasmodium: Deciphering its role for Eliminou: , was highlighted

    Received: 06 Jun 2024; Accepted: 08 Oct 2024.

    Copyright: © 2024 F. Gonçalves, Lima-Pinheiro and Ferreira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Adriana F. Gonçalves, Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal
    Pedro E. Ferreira, Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal

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