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Updated: Jul 27, 2025
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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
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Parasite proteostasis and artemisinin resistance
Melissa Rosenthal1, Caroline Ng1
1University of Nebraska Medical Center.
Research Square
|June 9, 2023
Summary
Artemisinin resistance in malaria threatens elimination efforts. Targeting the parasite unfolded protein response (UPR) and ubiquitin proteasome system (UPS) may overcome artemisinin resistance by restoring proteostasis.
Area of Science:
- Malariology
- Molecular Parasitology
- Drug Resistance
Background:
- Artemisinins are crucial antimalarials, but resistance threatens malaria elimination.
- Kelch13 mutations are linked to artemisinin resistance, potentially via altered activation or stress response.
- The parasite's proteostasis mechanisms, including the unfolded protein response (UPR) and ubiquitin proteasome system (UPS), are critical for survival.
Approach:
- Investigated the role of the UPR and UPS in artemisinin resistance.
- Examined the impact of perturbing parasite proteostasis on parasite viability.
- Assessed the correlation between artemisinin susceptibility and proteasome function.
Key Points:
- Disrupting parasite proteostasis leads to parasite death.
- Early UPR signaling significantly influences survival outcomes following dihydroartemisinin (DHA) treatment.
- Impaired proteasome-mediated protein degradation is associated with DHA susceptibility.
Conclusions:
- The UPR and UPS are integral to artemisinin resistance mechanisms.
- Targeting parasite proteostasis pathways offers a promising strategy to combat artemisinin resistance.
- Developing novel therapeutics that modulate the UPR and UPS could restore antimalarial efficacy.
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