ArticleHuman molecular genetics2015
Glutaredoxin deficiency exacerbates neurodegeneration in C. elegans models of Parkinson's disease.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- HSPBiomedicines · 2025Article
- Unraveling Molecular Targets for Neurodegenerative Diseases ThroughInternational journal of molecular sciences · 2025Review
- NRF1 mitigates motor dysfunction and dopamine neuron degeneration in mice with Parkinson's disease by promoting GLRX mCNS neuroscience & therapeutics · 2024Article
- Secretome Analyses Identify FKBP4 as aInternational journal of molecular sciences · 2024Article
- Repressor Element-1 Binding Transcription Factor (REST) as a Possible Epigenetic Regulator of Neurodegeneration and MicroRNA-Based Therapeutic Strategies.Molecular neurobiology · 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
- S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- S-Denitrosylation: A Crosstalk between Glutathione and Redoxin Systems.Antioxidants (Basel, Switzerland) · 2022Review
- Glutaredoxin: Discovery, redox defense and much more.Redox biology · 2021Review
- Article
- Modeling neurodegeneration inDisease models & mechanisms · 2020Review
- Redox RegulationAntioxidants & redox signaling · 2020Review
- The glutathione system and the related thiol network in Caenorhabditis elegans.Redox biology · 2019Review
- Critical Roles of Glutaredoxin in Brain Cells-Implications for Parkinson's Disease.Antioxidants & redox signaling · 2019Review
- Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System.Antioxidants & redox signaling · 2017Review
- Redox-based therapeutics in neurodegenerative disease.British journal of pharmacology · 2017Review
- From structure to redox: The diverse functional roles of disulfides and implications in disease.Proteomics · 2017Review
- Behavioral Phenotyping and Pathological Indicators of Parkinson's Disease inFrontiers in genetics · 2017Review
- Upregulation of Glutaredoxin-1 Activates Microglia and Promotes Neurodegeneration: Implications for Parkinson's Disease.Antioxidants & redox signaling · 2016Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic neurons. Although the etiology of PD remains incompletely understood, oxidative stress has been implicated as an important contributor in the development of PD. Oxidative stress can lead to oxidation and functional perturbation of proteins critical to neuronal survival. Glutaredoxin 1 (Grx1) is an evolutionally conserved antioxidant enzyme that repairs protein oxidation by reversing the oxidative modification of cysteine known as S-glutathionylation. We aimed to explore the regulatory role of Grx1 in PD. We first examined the levels of Grx1 in postmortem midbrain samples from PD patients, and observed that Grx1 content is decreased in PD, specifically within the dopaminergic neurons. We subsequently investigated the potential role of Grx1 deficiency in PD pathogenesis by examining the consequences of loss of the Caenorhabditis elegans Grx1 homolog in well-established worm models of familial PD caused by overexpression of pathogenic human LRRK2 mutants G2019S or R1441C. We found that loss of the Grx1 homolog led to significant exacerbation of the neurodegenerative phenotype in C. elegans overexpressing the human LRRK2 mutants. Re-expression in the dopaminergic neurons of the active, but not a catalytically inactive form of the Grx1 homolog rescued the exacerbated phenotype. Loss of the Grx1 homolog also exacerbated the neurodegenerative phenotype in other C. elegans models, including overexpression of human α-synuclein and overexpression of tyrosine hydroxylase (a model of sporadic PD). Therefore, our results reveal a novel neuroprotective role of glutaredoxin against dopaminergic neurodegeneration in models of familial and sporadic PD.
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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.