ArticleAnnals of neurology2011
N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1-/- mouse.
Article in Annals of neurology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- N-acetylcysteine for Parkinson's disease: a translational systematic review of mechanistic and early clinical data.Neurodegenerative disease management · 2026Pooled it
- Lineage-Dependent Regulation of Glutathione Homeostasis by EAAC1 and GTRAP3-18 During Differentiation of Mesenchymal Stem Cells into Neuron-like Cells.International journal of molecular sciences · 2026Article
- Plasma EAAT2 and GABA as candidate biomarkers in males with autism spectrum disorder: an exploratory case-control study with ROC analysis.Scientific reports · 2026Article
- Organosulfur Compounds: Potential Therapeutics for Parkinson's Disease.CNS & neurological disorders drug targets · 2026Review
- Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.Genome medicine · 2025Article
- The Central Nervous System Modulatory Activities of N-Acetylcysteine: A Synthesis of Two Decades of Evidence.Current issues in molecular biology · 2025Review
- Current trends and future prospects of N-acetylcysteine utilizations in Parkinson's disease: A literature network analysis.Journal of Taibah University Medical Sciences · 2025Review
- Article
- Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson's Disease.International journal of molecular sciences · 2024Review
- Targeting the Cysteine Redox Proteome in Parkinson's Disease: The Role of Glutathione Precursors and Beyond.Antioxidants (Basel, Switzerland) · 2023Review
- N-Acetylcysteine Treatment May Compensate Motor Impairments through Dopaminergic Transmission Modulation in a Striatal 6-Hydroxydopamine Parkinson's Disease Rat Model.Antioxidants (Basel, Switzerland) · 2023Article
- Symport and antiport mechanisms of human glutamate transporters.Nature communications · 2023Article
- Article
- Neuronal Oxidative Stress Promotes α-Synuclein Aggregation In Vivo.Antioxidants (Basel, Switzerland) · 2022Article
- Bilirubin Prevents the THInternational journal of molecular sciences · 2022Article
- α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans.Progress in neurobiology · 2022Article
- Nitrosative stress in Parkinson's disease.NPJ Parkinson's disease · 2022Review
- From regenerative strategies to pharmacological approaches: can we fine-tune treatment for Parkinson's disease?Neural regeneration research · 2022Article
- Developmental impact of glutamate transporter overexpression on dopaminergic neuron activity and stereotypic behavior.Molecular psychiatry · 2022Article
- Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveDopaminergic neuronal death in Parkinson's disease (PD) is accompanied by oxidative stress and preceded by glutathione depletion. The development of disease-modifying therapies for PD has been hindered by a paucity of animal models that mimic these features and demonstrate an age-related progression. The EAAC1(-/-) mouse may be useful in this regard, because EAAC1(-/-) mouse neurons have impaired neuronal cysteine uptake, resulting in reduced neuronal glutathione content and chronic oxidative stress. Here we aimed to (1) characterize the age-related changes in nigral dopaminergic neurons in the EAAC1(-/-) mouse, and (2) use the EAAC1(-/-) mouse to evaluate N-acetylcysteine, a membrane-permeable cysteine pro-drug, as a potential disease-modifying intervention for PD.
methodsWild-type mice, EAAC1(-/-) mice, and EAAC1(-/-) mice chronically treated with N-acetylcysteine were evaluated at serial time points for evidence of oxidative stress, dopaminergic cell death, and motor abnormalities.
resultsEAAC1(-/-) mice showed age-dependent loss of dopaminergic neurons in the substantia nigra pars compacta, with more than 40% of these neurons lost by age 12 months. This neuronal loss was accompanied by increased nitrotyrosine formation, nitrosylated α-synuclein, and microglial activation. These changes were substantially reduced in mice that received N-acetylcysteine.
interpretationThese findings suggest that the EAAC1(-/-) mouse may be a useful model of the chronic neuronal oxidative stress that occurs in PD. The salutary effects of N-acetylcysteine in this mouse model provide an impetus for clinical evaluation of glutathione repletion in PD.
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Registered trials
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