ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Human immunodeficiency virus type 1 alters brain-derived neurotrophic factor processing in neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Resistance Training Improves Cognitive Function and Depression Without Changing BDNF Levels in People Living with HIV: a Randomized Controlled Clinical Trial.AIDS and behavior · 2025Trial
- Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial.Journal of neurovirology · 2023Trial
- Review
- Cannabis use by people with HIV is associated with an anti-inflammatory immunometabolic phenotype in monocyte-derived macrophages.Journal of neuroinflammation · 2026Article
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Human immunodeficiency virus 1 glycoprotein 120 induces endoplasmic reticulum stress in neurons.Cell death & disease · 2025Article
- Serum Mature and Precursor Brain-Derived Neurotrophic Factors and Their Association with Neurocognitive Function in ART-Naïve Adults Living with HIV in Sub-Saharan Africa.Molecular neurobiology · 2025Article
- The Association Between Serum Mature and Precursor Brain-Derived Neurotrophic Factor and Neurocognitive Function in People With Human Immunodeficiency Virus: A Longitudinal Study.Open forum infectious diseases · 2024Article
- Accelerated neurodegeneration of basal forebrain cholinergic neurons in HIV-1 gp120 transgenic mice: Critical role of the p75 neurotrophin receptor.Brain, behavior, and immunity · 2024Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status.International journal of molecular sciences · 2023Article
- The Association Between Objectively-Measured Physical Activity and Cognitive Functioning in Middle-Aged and Older People Living with HIV.AIDS and behavior · 2023Article
- HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.Cellular and molecular neurobiology · 2022Review
- Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System.International journal of molecular sciences · 2022Review
- Recent Advances in the Molecular and Cellular Mechanisms of gp120-Mediated Neurotoxicity.Cells · 2022Review
- Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model.Communications biology · 2022Article
- HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein.Frontiers in aging neuroscience · 2022Article
- Race-Dependent Association of Single-Nucleotide Polymorphisms in TrkB Receptor in People Living with HIV and Depression.Neurotoxicity research · 2021Article
- Extracellular Vesicles and HIV-Associated Neurocognitive Disorders: Implications in Neuropathogenesis and Disease Diagnosis.Neurotoxicity research · 2021Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The molecular mechanisms leading to synaptic simplification and neuronal apoptosis in human immunodeficiency virus type 1 (HIV-1)-positive subjects are unknown. The HIV protein gp120 reduced the length of neuronal processes similarly to the proneurotrophin pro-brain-derived neurotrophic factor (proBDNF). Intriguingly, the effects of both proBDNF and gp120 were blocked by inhibitors of the p75 neurotrophin receptor, suggesting that proBDNF and gp120 share a similar mechanism of neurotoxicity. Therefore, we tested the hypothesis that gp120 affects the release of proBDNF. Using rat primary neurons, we observed that gp120 promotes a time-dependent intracellular and extracellular accumulation of proBDNF concomitantly with a decrease in mature BDNF. A similar imbalance in the ratio proBDNF/mature BDNF was confirmed in postmortem brains of HIV-positive subjects cognitively impaired and motor impaired. Therefore, it is conceivable to formulate the hypothesis that HIV neurotoxicity includes a gp120-mediated alteration of BDNF processing. To determine the cellular mechanism whereby gp120 produces an accumulation of proBDNF, we examined the levels of intracellular and extracellular enzymes that proteolytically cleave proBDNF furin and tissue plasminogen, respectively. In rat neurons exposed to gp120, intracellular furin levels decreased before cell death, whereas tissue plasminogen changed only during apoptosis. Our data suggest that HIV, through gp120, reduces proBDNF processing by affecting furin levels, and therefore causes an altered balance between antiapoptotic and proapoptotic neurotrophins. Our studies identify a new mechanism that may explain how HIV promotes neuronal injury.
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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.