ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Glutaminase dysregulation in HIV-1-infected human microglia mediates neurotoxicity: relevant to HIV-1-associated neurocognitive disorders.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Pooled it
- Protocol to generate microglia-containing cerebral organoids to model HIV neuroinflammation.STAR protocols · 2026Article
- Structure and enzymology of glutaminase S482C and H461L variants associated with excess brain glutamate and neurological disease.The Journal of biological chemistry · 2026Article
- Tuberculous meningitis alters the proteomic landscape of brain-derived extracellular vesicles.bioRxiv : the preprint server for biology · 2025Article
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Structure and enzymology of glutaminase mutants that disrupt glutamine-glutamate homeostasis and cause neurological disease.bioRxiv : the preprint server for biology · 2025Article
- Review
- Minocycline AmelioratesBrain sciences · 2025Article
- Tissue-resident immune cells: from defining characteristics to roles in diseases.Signal transduction and targeted therapy · 2025Review
- Dual immune modulation of microglia in viral encephalitis: current understanding and future perspectives.Frontiers in molecular biosciences · 2025Review
- Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.Aging and disease · 2024Review
- Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection.Molecular neurobiology · 2024Review
- Neurological impact of HIV/AIDS and substance use alters brain function and structure.Frontiers in medicine · 2024Review
- Behavioral and histological assessment of a novel treatment of neuroHIV in humanized mice.Research square · 2023Article
- Microglial Metabolic Reprogramming: Emerging Insights and Therapeutic Strategies in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2023Review
- Therapeutically targeting the consequences of HIV-1-associated gastrointestinal dysbiosis: Implications for neurocognitive and affective alterations.Pharmacology, biochemistry, and behavior · 2023Article
- Human microglial models to study host-virus interactions.Experimental neurology · 2023Review
- Tissue-resident immune cells in the pathogenesis of multiple sclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- A new perspective on HIV: effects of HIV on brain-heart axis.Frontiers in cardiovascular medicine · 2023Review
- Microglia activation in the mPFC mediates anxiety-like behaviors caused by Staphylococcus aureus strain USA300.Brain and behavior · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Microglia represent the main cellular targets of HIV-1 in the brain. Infected and/or activated microglia play a pathogenic role in HIV-associated neurocognitive disorders (HAND) by instigating primary dysfunction and subsequent death of neurons. Although microglia are known to secrete neurotoxins when infected with HIV-1, the detailed mechanism of neurotoxicity remains unclear. Using a human microglia primary culture system and macrophage-tropic HIV-1 strains, we have now demonstrated that HIV-1 infection of microglia resulted in a significant increase in extracellular glutamate concentrations and elevated levels of neurotoxicity. RNA and protein analysis revealed upregulation of the glutamate-generating enzyme glutaminase isoform glutaminase C in HIV-1-infected microglia. The clinical relevance of these findings was further corroborated with investigation of postmortem brain tissues. The glutaminase C levels in the brain tissues of HIV dementia individuals were significantly higher than HIV serum-negative control and correlated with elevated concentrations of glutamate. When glutaminase was subsequently inhibited by siRNA or by a small molecular inhibitor, the HIV-induced glutamate production and the neuronal loss was diminished. In conclusion, these findings support glutaminase as a potential component of the HAND pathogenic process as well as a novel therapeutic target in their treatment.
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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.