ArticleJournal of neuroinflammation2016
Pyrrolidine dithiocarbamate activates the Nrf2 pathway in astrocytes.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 52 citations in OpenAlex.
- Role for NF-κB in herpes encephalitis pathology in mice genocopying an inborn error of IRF3-IFN immunity.The Journal of experimental medicine · 2026Article
- Bioadaptive liquid-infused multifunctional fibers for long-term neural recording via BDNF stabilization and enhanced neural interaction.Science advances · 2025Article
- Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway.Neurochemical research · 2024Article
- Microglial ferroptotic stress causes non-cell autonomous neuronal death.Molecular neurodegeneration · 2024Article
- NRF2 Activation by Nitrogen Heterocycles: A Review.Molecules (Basel, Switzerland) · 2023Review
- Nrf2 is predominantly expressed in hippocampal neurons in a rat model of temporal lobe epilepsy.Cell & bioscience · 2023Article
- NF-κB and AP-1 are required for the lipopolysaccharide-induced expression of MCP-1, CXCL1, and Cx43 in cultured rat dorsal spinal cord astrocytes.Frontiers in molecular neuroscience · 2022Article
- The Menadione-Mediated WST1 Reduction by Cultured Astrocytes Depends on NQO1 Activity and Cytosolic Glucose Metabolism.Neurochemical research · 2021Article
- Physiological Concentration of HCellular and molecular neurobiology · 2021Article
- Targeting of Perforin Inhibitor into the Brain Parenchyma Via a Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation and Improve Cell Survival.Molecular neurobiology · 2020Article
- L-Type Amino Acid Transporter 1 (LAT1/Lat1)-Utilizing Prodrugs Can Improve the Delivery of Drugs into Neurons, Astrocytes and Microglia.Scientific reports · 2019Article
- Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats.BMC anesthesiology · 2019Article
- Astrocyte-Targeted Transporter-Utilizing Derivatives of Ferulic Acid Can Have Multifunctional Effects Ameliorating Inflammation and Oxidative Stress in the Brain.Oxidative medicine and cellular longevity · 2019Article
- Acute dose of melatonin via Nrf2 dependently prevents acute ethanol-induced neurotoxicity in the developing rodent brain.Journal of neuroinflammation · 2018Article
- Downregulated Nuclear Factor E2-Related Factor 2 (Nrf2) Aggravates Cognitive Impairments via Neuroinflammation and Synaptic Plasticity in the Senescence-Accelerated Mouse Prone 8 (SAMP8) Mouse: A Model of Accelerated Senescence.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-κB Signaling Pathway.Frontiers in cellular neuroscience · 2018Article
- Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?Antioxidants (Basel, Switzerland) · 2017Review
- Delayed Nrf2-regulated antioxidant gene induction in response to silica nanoparticles.Free radical biology & medicine · 2017Article
- Potential dual role of nuclear factor-kappa B in experimental subarachnoid hemorrhage-induced early brain injury in rabbits.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Article
- Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.Inflammopharmacology · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndogenous defense against oxidative stress is controlled by nuclear factor erythroid 2-related factor 2 (Nrf2). The normal compensatory mechanisms to combat oxidative stress appear to be insufficient to protect against the prolonged exposure to reactive oxygen species during disease. Counterbalancing the effects of oxidative stress by up-regulation of Nrf2 signaling has been shown to be effective in various disease models where oxidative stress is implicated, including Alzheimer's disease. Stimulation of Nrf2 signaling by small-molecule activators is an appealing strategy to up-regulate the endogenous defense mechanisms of cells.
methodsHere, we investigate Nrf2 induction by the metal chelator and known nuclear factor-κB inhibitor pyrrolidine dithiocarbamate (PDTC) in cultured astrocytes and neurons, and mouse brain. Nrf2 induction is further examined in cultures co-treated with PDTC and kinase inhibitors or amyloid-beta, and in Nrf2-deficient cultures.
resultsWe show that PDTC is a potent inducer of Nrf2 signaling specifically in astrocytes and demonstrate the critical role of Nrf2 in PDTC-mediated protection against oxidative stress. This induction appears to be regulated by both Keap1 and glycogen synthase kinase 3β. Furthermore, the presence of amyloid-beta magnifies PDTC-mediated induction of endogenous protective mechanisms, therefore suggesting that PDTC may be an effective Nrf2 inducer in the context of Alzheimer's disease. Finally, we show that PDTC increases brain copper content and glial expression of heme oxygenase-1, and decreases lipid peroxidation in vivo, promoting a more antioxidative environment.
conclusionsPDTC activates Nrf2 and its antioxidative targets in astrocytes but not neurons. These effects may contribute to the neuroprotection observed for PDTC in models of Alzheimer's disease.
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