ArticleProceedings of the National Academy of Sciences of the United States of America2015
Targeting glutamine metabolism rescues mice from late-stage cerebral malaria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 78 citations in OpenAlex.
- Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria.Nature immunology · 2020Trial
- CD8+ T cells target cerebrovasculature in children with cerebral malaria.The Journal of clinical investigation · 2020Trial
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Malaria and cancer: common features and interactions.Trends in parasitology · 2026Review
- Safety, Tolerability, and Pharmacokinetics of 6-Diazo-5-Oxo-L-Norleucine in Malawian Adults With and Without Malaria: A Phase 1 Dose-Escalation Clinical Trial.The Journal of infectious diseases · 2026Article
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Unveiling new perspectives about the onset of neurological and cognitive deficits in cerebral malaria: exploring cellular and neurochemical mechanisms.Frontiers in cellular and infection microbiology · 2025Review
- Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.PLoS pathogens · 2025Review
- Time of day and circadian disruption influence host response and parasite growth in a mouse model of cerebral malaria.iScience · 2024Article
- Host metabolomic responses in recurrent P. vivax malaria.Scientific reports · 2024Article
- The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024Review
- Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cells.Cell metabolism · 2024Article
- DON in pediatric cerebral malaria, a phase I/IIA dose-escalation safety study: study protocol for a clinical trial.Trials · 2024Article
- Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024Review
- Ubiquitination in the T Cell Metabolism-Based Immunotherapy in Diseases.Advances in experimental medicine and biology · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Article
- Modeling infectious diseases of the central nervous system with human brain organoids.Translational research : the journal of laboratory and clinical medicine · 2022Review
- An update on cerebral malaria for therapeutic intervention.Molecular biology reports · 2022Review
- Hypothyroidism confers tolerance to cerebral malaria.Science advances · 2022Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
The most deadly complication of Plasmodium falciparum infection is cerebral malaria (CM) with a case fatality rate of 15-25% in African children despite effective antimalarial chemotherapy. There are no adjunctive treatments for CM, so there is an urgent need to identify new targets for therapy. Here we show that the glutamine analog 6-diazo-5-oxo-L-norleucine (DON) rescues mice from CM when administered late in the infection a time at which mice already are suffering blood-brain barrier dysfunction, brain swelling, and hemorrhaging accompanied by accumulation of parasite-specific CD8(+) effector T cells and infected red blood cells in the brain. Remarkably, within hours of DON treatment mice showed blood-brain barrier integrity, reduced brain swelling, decreased function of activated effector CD8(+) T cells in the brain, and levels of brain metabolites that resembled those in uninfected mice. These results suggest DON as a strong candidate for an effective adjunctive therapy for CM in African children.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.