ArticlePloS one2012
Dysregulation of macrophage-secreted cathepsin B contributes to HIV-1-linked neuronal apoptosis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Risk factors for HIV-associated neurocognitive impairment and frailty in aging people with HIV in Latin America: a systematic review.BMC neurology · 2026Pooled it
- HIV Tat-activated microglial extracellular vesicles induce neuronal iron dysregulation and synaptodendritic injury.Cell communication and signaling : CCS · 2026Article
- Cannabinoid Receptor Type 2 Agonist JWH-133 Stimulates Antiviral Factors and Decreases Proviral, Inflammatory, and Neurotoxic Proteins in HIV-Infected Macrophage Secretome.International journal of molecular sciences · 2025Article
- Article
- Single-cell analysis of CD14Frontiers in immunology · 2025Article
- Analysis of Sigma-1 Receptor Antagonist BD1047 Effect on Upregulating Proteins in HIV-1-Infected Macrophages Exposed to Cocaine Using Quantitative Proteomics.Biomedicines · 2024Article
- Quantitative Proteomics Reveal That CB2R Agonist JWH-133 Downregulates NF-κB Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages.International journal of molecular sciences · 2024Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Cathepsin B Gene Knockout Improves Behavioral Deficits and Reduces Pathology in Models of Neurologic Disorders.Pharmacological reviews · 2022Review
- Inhibition of Cathepsin B and SAPC Secreted by HIV-Infected Macrophages Reverses Common and Unique Apoptosis Pathways.Journal of proteome research · 2022Article
- Cannabinoid receptor type 2 agonist JWH-133 decreases cathepsin B secretion and neurotoxicity from HIV-infected macrophages.Scientific reports · 2022Article
- The role of Pannexin-1 channels and extracellular ATP in the pathogenesis of the human immunodeficiency virus.Purinergic signalling · 2021Review
- Extracellular Vesicles and HIV-Associated Neurocognitive Disorders: Implications in Neuropathogenesis and Disease Diagnosis.Neurotoxicity research · 2021Review
- Altered expression of fractalkine in HIV-1-infected astrocytes and consequences for the virus-related neurotoxicity.Journal of neurovirology · 2021Article
- Targeting Macrophage Dysregulation for Viral Infections: Novel Targets for Immunomodulators.Frontiers in immunology · 2021Review
- Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis.Cell reports · 2020Article
- Potential pharmacological approaches for the treatment of HIV-1 associated neurocognitive disorders.Fluids and barriers of the CNS · 2020Review
- Penetrating Traumatic Brain Injury Triggers Dysregulation of Cathepsin B Protein Levels Independent of Cysteine Protease Activity in Brain and Cerebral Spinal Fluid.Journal of neurotrauma · 2020Article
- Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?Frontiers in cellular and infection microbiology · 2020Review
- HIV-induced neuroinflammation: impact of PAR1 and PAR2 processing by Furin.Cell death and differentiation · 2019Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic HIV infection leads to the development of cognitive impairments, designated as HIV-associated neurocognitive disorders (HAND). The secretion of soluble neurotoxic factors by HIV-infected macrophages plays a central role in the neuronal dysfunction and cell death associated with HAND. One potentially neurotoxic protein secreted by HIV-1 infected macrophages is cathepsin B. To explore the potential role of cathepsin B in neuronal cell death after HIV infection, we cultured HIV-1(ADA) infected human monocyte-derived macrophages (MDM) and assayed them for expression and activity of cathepsin B and its inhibitors, cystatins B and C. The neurotoxic activity of the secreted cathepsin B was determined by incubating cells from the neuronal cell line SK-N-SH with MDM conditioned media (MCM) from HIV-1 infected cultures. We found that HIV-1 infected MDM secreted significantly higher levels of cathepsin B than did uninfected cells. Moreover, the activity of secreted cathepsin B was significantly increased in HIV-infected MDM at the peak of viral production. Incubation of neuronal cells with supernatants from HIV-infected MDM resulted in a significant increase in the numbers of apoptotic neurons, and this increase was reversed by the addition of either the cathepsin B inhibitor CA-074 or a monoclonal antibody to cathepsin B. In situ proximity ligation assays indicated that the increased neurotoxic activity of the cathepsin B secreted by HIV-infected MDM resulted from decreased interactions between the enzyme and its inhibitors, cystatins B and C. Furthermore, preliminary in vivo studies of human post-mortem brain tissue suggested an upregulation of cathepsin B immunoreactivity in the hippocampus and basal ganglia in individuals with HAND. Our results demonstrate that HIV-1 infection upregulates cathepsin B in macrophages, increases cathepsin B activity, and reduces cystatin-cathepsin interactions, contributing to neuronal apoptosis. These findings provide new evidence for the role of cathepsin B in neuronal cell death induced by HIV-infected macrophages.
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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.