ArticleAntioxidants & redox signaling2016
Upregulation of Glutaredoxin-1 Activates Microglia and Promotes Neurodegeneration: Implications for Parkinson's Disease.
Article in Antioxidants & redox signaling, 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, 40 citations in OpenAlex.
- Repressor Element-1 Binding Transcription Factor (REST) as a Possible Epigenetic Regulator of Neurodegeneration and MicroRNA-Based Therapeutic Strategies.Molecular neurobiology · 2023Review
- Glutaredoxin attenuates glutathione levels via deglutathionylation of Otub1 and subsequent destabilization of system xScience advances · 2023Article
- Glutathione and Glutaredoxin-Key Players in Cellular Redox Homeostasis and Signaling.Antioxidants (Basel, Switzerland) · 2023Review
- Critical Roles of the Cysteine-Glutathione Axis in the Production of γ-Glutamyl Peptides in the Nervous System.International journal of molecular sciences · 2023Review
- Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies.Antioxidants (Basel, Switzerland) · 2023Review
- Review
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- Role of CD40(L)-TRAF signaling in inflammation and resolution-a double-edged sword.Frontiers in pharmacology · 2022Review
- Thiol Modifications in the Extracellular Space-Key Proteins in Inflammation and Viral Infection.Frontiers in immunology · 2022Review
- Glutaredoxin: Discovery, redox defense and much more.Redox biology · 2021Review
- Glutaredoxin 1 regulates macrophage polarization through mediating glutathionylation of STAT1.Thoracic cancer · 2020Article
- Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Redox RegulationAntioxidants & redox signaling · 2020Review
- Endothelial cell-specific redox gene modulation inhibits angiogenesis but promotes B16F0 tumor growth in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Critical Roles of Glutaredoxin in Brain Cells-Implications for Parkinson's Disease.Antioxidants & redox signaling · 2019Review
- Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease.Oxidative medicine and cellular longevity · 2019Review
- Article
- European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).Redox biology · 2017Review
- Redox regulation of ischemic limb neovascularization - What we have learned from animal studies.Redox biology · 2017Review
- Novel chloroacetamido compound CWR-J02 is an anti-inflammatory glutaredoxin-1 inhibitor.PloS one · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
aimsNeuroinflammation and redox dysfunction are recognized factors in Parkinson's disease (PD) pathogenesis, and diabetes is implicated as a potentially predisposing condition. Remarkably, upregulation of glutaredoxin-1 (Grx1) is implicated in regulation of inflammatory responses in various disease contexts, including diabetes. In this study, we investigated the potential impact of Grx1 upregulation in the central nervous system on dopaminergic (DA) viability.
resultsIncreased GLRX copy number in PD patients was associated with earlier PD onset, and Grx1 levels correlated with levels of proinflammatory tumor necrosis factor-alpha (TNF-α) in mouse and human brain samples, prompting mechanistic in vitro studies. Grx1 content/activity in microglia was upregulated by lipopolysaccharide (LPS), or TNF-α, treatment. Adenoviral overexpression of Grx1, matching the extent of induction by LPS, increased microglial activation; Grx1 silencing diminished activation. Selective inhibitors/probes of nuclear factor κB (NF-κB) activation revealed glrx1 induction to be mediated by the Nurr1/NF-κB axis. Upregulation of Grx1 in microglia corresponded to increased death of neuronal cells in coculture. With a mouse diabetes model of diet-induced insulin resistance, we found upregulation of Grx1 in brain was associated with DA loss (decreased tyrosine hydroxylase [TH]; diminished TH-positive striatal axonal terminals); these effects were not seen with Grx1-knockout mice. INNOVATION: Our results indicate that Grx1 upregulation promotes neuroinflammation and consequent neuronal cell death in vitro, and synergizes with proinflammatory insults to promote DA loss in vivo. Our findings also suggest a genetic link between elevated Grx1 and PD development.
conclusionIn vitro and in vivo data suggest Grx1 upregulation promotes neurotoxic neuroinflammation, potentially contributing to PD. Antioxid. Redox Signal. 25, 967-982.
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