ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2016
Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04964843 (A Pilot Study of N-acetylcysteine for Alcohol Use Disorder), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Pilot Study of N-acetylcysteine for Alcohol Use Disorder
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- N-acetylcysteine for Parkinson's disease: a translational systematic review of mechanistic and early clinical data.Neurodegenerative disease management · 2026Pooled it
- N-Acetylcysteine Reduces Tissue Injury Induced by Oxygen-Glucose Deprivation in an Organotypic Culture of Mouse Cerebral Cortex Slices.Children (Basel, Switzerland) · 2026Article
- High-Frequency, Low-Intensity Pulsed Electric Field and N-Acetylcysteine Synergistically Protect SH-SY5Y Cells Against Hydrogen Peroxide-Induced Cell Damage In Vitro.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- Exploring the Causal Links Between 338 Cerebrospinal Fluid Metabolites and Parkinson's Disease.Brain and behavior · 2025Article
- Cracking the Code of Oocyte Quality: The Oxidative Stress Link to IVF Success.International journal of molecular sciences · 2025Review
- Reciprocal regulation of oxidative stress and mitochondrial fission augments parvalbumin downregulation through CDK5-DRP1- and GPx1-NF-κB signaling pathways.Cell death & disease · 2024Article
- Aluminum enhances the oxidative damage of ZnO NMs in the human neuroblastoma SH-SY5Y cell line.Discover nano · 2024Article
- Curcumin and N-Acetylcysteine Nanocarriers Alone or Combined with Deferoxamine Target the Mitochondria and Protect against Neurotoxicity and Oxidative Stress in a Co-Culture Model of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2023Article
- Neuronal Oxidative Stress Promotes α-Synuclein Aggregation In Vivo.Antioxidants (Basel, Switzerland) · 2022Article
- The Prevention and Reversal of a Phenytoin-Resistant Model by N-acetylcysteine Therapy Involves the Nrf2/P-Glycoprotein Pathway at the Blood-Brain Barrier.Journal of molecular neuroscience : MN · 2022Article
- α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans.Progress in neurobiology · 2022Article
- Glutathione Regulates GPx1 Expression during CA1 Neuronal Death and Clasmatodendrosis in the Rat Hippocampus following Status Epilepticus.Antioxidants (Basel, Switzerland) · 2022Article
- α-synuclein aggregates induce c-Abl activation and dopaminergic neuronal loss by a feed-forward redox stress mechanism.Progress in neurobiology · 2021Article
- Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry.Molecular neurobiology · 2021Review
- Protective Effect of γ-mangostin Isolated from the Peel ofBiomolecules · 2021Article
- Potential Roles of Redox Dysregulation in the Development of Schizophrenia.Biological psychiatry · 2020Review
- N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2020Article
- Histomorphological evaluations on the frontal cortex extrapyramidal cell layer following administration of N-Acetyl cysteine in aluminum induced neurodegeneration rat model.Metabolic brain disease · 2020Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
N-acetyl cysteine (NAC) supports the synthesis of glutathione (GSH), an essential substrate for fast, enzymatically catalyzed oxidant scavenging and protein repair processes. NAC is entering clinical trials for adrenoleukodystrophy, Parkinson's disease, schizophrenia, and other disorders in which oxidative stress may contribute to disease progression. However, these trials are hampered by uncertainty about the dose of NAC required to achieve biological effects in human brain. Here we describe an approach to this issue in which mice are used to establish the levels of NAC in cerebrospinal fluid (CSF) required to affect brain neurons. NAC dosing in humans can then be calibrated to achieve these NAC levels in human CSF. The mice were treated with NAC over a range of doses, followed by assessments of neuronal GSH levels and neuronal antioxidant capacity in ex vivo brain slices. Neuronal GSH levels and antioxidant capacity were augmented at NAC doses that produced peak CSF NAC concentrations of ≥50 nM. Oral NAC administration to humans produced CSF concentrations of up to 10 μM, thus demonstrating that oral NAC administration can surpass the levels required for biological activity in brain. Variations of this approach may similarly facilitate and rationalize drug dosing for other agents targeting central nervous system disorders.
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Registered trials
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.