ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2019
Glutamine Antagonist JHU083 Normalizes Aberrant Glutamate Production and Cognitive Deficits in the EcoHIV Murine Model of HIV-Associated Neurocognitive Disorders.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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32 citing papers in PubMed, 43 citations in OpenAlex.
- Glutamine antagonist DON attenuates chikungunya virus-induced myositis by suppressing inflammatory activation in a murine model.Emerging microbes & infections · 2026Article
- Sex-specific gut mycobiome dysbiosis activates macrophage dectin-1 signaling to drive neurobehavioral deficits in EcoHIV-infected mice.Brain, behavior, and immunity · 2026Article
- Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment.Med (New York, N.Y.) · 2026Article
- CXCL11 levels regulate lung Treg responses to deter the onset of HIV-related COPD.Respiratory research · 2026Article
- Targeting NAAG metabolism restores cognition and synaptic integrity in EcoHIV-infected mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Inhibiting Glycan Degradation Prevents HIV-Induced Inflammaging and Cognitive Impairment.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
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- Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.Aging and disease · 2024Review
- EcoHIV Infection of Primary Murine Brain Cell Cultures to Model HIV Replication and Neuropathogenesis.Viruses · 2024Article
- Role of glutamine metabolism in tuberculosis pathogenesis: a mini review.Frontiers in tuberculosis · 2024Review
- Innate immune responses reverse HIV cognitive disease in mice: Profile by RNAseq in the brain.Virology · 2024Article
- Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis.Nature communications · 2023Article
- Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication.Nature communications · 2023Article
- Microglial-Targeted nSMase2 Inhibitor Fails to Reduce Tau Propagation in PS19 Mice.Pharmaceutics · 2023Article
- A gut-restricted glutamate carboxypeptidase II inhibitor reduces monocytic inflammation and improves preclinical colitis.Science translational medicine · 2023Article
- CCL2 is required for initiation but not persistence of HIV infection mediated neurocognitive disease in mice.Scientific reports · 2023Article
- Article
- Human iPSC-derived neurons reveal NMDAR-independent dysfunction following HIV-associated insults.Frontiers in molecular neuroscience · 2023Article
- A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment.Microorganisms · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
HIV-associated neurocognitive disorders (HAND) have been linked to dysregulation of glutamate metabolism in the central nervous system (CNS) culminating in elevated extracellular glutamate and disrupted glutamatergic neurotransmission. Increased glutamate synthesis via upregulation of glutaminase (GLS) activity in brain immune cells has been identified as one potential source of excess glutamate in HAND. However, direct evidence for this hypothesis in an animal model is lacking, and the viability of GLS as a drug target has not been explored. In this brief report, we demonstrate that GLS inhibition with the glutamine analogue 6-diazo-5-oxo-L-norleucine (DON) can reverse cognitive impairment in the EcoHIV-infected mouse model of HAND. However, due to peripheral toxicity DON is not amenable to clinical use in a chronic disease such as HAND. We thus tested JHU083, a novel, brain penetrant DON prodrug predicted to exhibit improved tolerability. Systemic administration of JHU083 reversed cognitive impairment in EcoHIV-infected mice similarly to DON, and simultaneously normalized EcoHIV-induced increases in cerebrospinal fluid (CSF) glutamate and GLS activity in microglia-enriched brain CD11b + cells without observed toxicity. These studies support the mechanistic involvement of elevated microglial GLS activity in HAND pathogenesis, and identify JHU083 as a potential treatment option. Graphical Abstract Please provide Graphical Abstract caption.Glutamine Antagonist JHU083 Normalizes Aberrant Glutamate Production and Cognitive Deficits in the EcoHIV Murine Model of HIV-Associated Neurocognitive Disorders .
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