The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
N-acetylcysteine Boosts Brain and Blood Glutathione in Gaucher and Parkinson Diseases
Open accessAbstract
OBJECTIVE: This study aimed to determine if the antioxidant N-acetylcysteine (NAC) is able to alter peripheral and central redox capabilities in patients with Parkinson disease (PD) or Gaucher disease (GD). METHODS: The study included nondemented adult subjects: 3 with PD, 3 with GD, and 3 healthy controls. Baseline brain glutathione (GSH) concentrations were measured using 7-T magnetic resonance spectroscopy (MRS). Baseline blood reduced-to-oxidized GSH ratios were determined for each subject. Brain GSH concentrations and blood redox ratios were then determined during and at specified time points after a single, 150-mg/kg NAC infusion. RESULTS: N-acetylcysteine increased blood GSH redox ratios in those with PD and GD and healthy controls, which was followed by an increase in brain GSH concentrations in all subjects. CONCLUSIONS: This is the first demonstration that with MRS, it is possible to directly measure and monitor increases in brain GSH levels in the human brain in response to a single, intravenous administration of NAC. This work shows the potential utility of MRS monitoring, which could assist in determining dosing regimens for clinical trials of this potentially useful antioxidant therapy for PD disease, GD, and other neurodegenerative disorders.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In a trial with patients suffering from PD was glutathione (GSH) level quantitatively monitored by Magnetic Resonance Imaging (MRI) following intravenously administrated 150 mg/kg of NAC. In all studied subjects the level of GSH increased, however, returned back to its original level after 120 min (Holmay et al. 2013).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Holmay et al. 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease
Sidransky, E., Nalls, M. A., Aasly, J. O., Aharon-Peretz, J., Annesi, G., Barbosa, E. R., Bar-Shira, A., Berg, D., Bras, J., Brice, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0901281 · Cited by 2,135
Oxidative stress in Parkinson's disease
Jenner, P. (2003) · Annals of Neurology · doi:10.1002/ana.10483 · Cited by 2,053
Metabolism and functions of glutathione in brain
Dringen, R. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00060-x · Cited by 1,702
Proton NMR chemical shifts and coupling constants for brain metabolites
Govindaraju, V., Young, K., & Maudsley, A. A. (2000) · NMR in Biomedicine · doi:10.1002/1099-1492(200005)13:3 · Cited by 1,695
Automatic quantitation of localized in vivo1H spectra with LCModel
Provencher, S. W. (2001) · NMR in Biomedicine · doi:10.1002/nbm.698 · Cited by 1,640
Sian, J., Dexter, D. T., Lees, A. J., Daniel, S., Agid, Y., Javoy‐Agid, F., Jenner, P., & Marsden, C. D. (1994) · Annals of Neurology · doi:10.1002/ana.410360305 · Cited by 1,161 · cited 4×
“In this study, we focused on the occipital cortex rather than the substantia nigra, where a GSH deficit has been detected postmortem in PD.(1) Because of challenges associated with MRS in the substantia nigra in humans, including its location, very small size (limiting signal-to-noise ratio), and high iron content (gi…”
BackgroundInfluentialBeal, M. F. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00780-3 · Cited by 763
Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse
Aoyama, K., Suh, S. W., Hamby, A. M., Liu, J., Chan, W. Y., Chen, Y., & Swanson, R. A. (2006) · Nature Neuroscience · doi:10.1038/nn1609 · Cited by 484
Analysis of macromolecule resonances in 1 H NMR spectra of human brain
Behar, K. L., Rothman, D. L., Spencer, D. D., & Petroff, O. A. C. (1994) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910320304 · Cited by 468 · cited 1×
“680 seconds).(24) Metabolites quantified with Cramér-Rao lower bounds (estimated error of the metabolite quantification) greater than 50% or correlation coefficient less than −0.”
MethodGrant, J. E., Odlaug, B. L., & Won Kim, S. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.60 · Cited by 424 · cited 1×
“There are reports of positive effects of oral NAC in disorders with central nervous system involvement.(29,30) Future studies are necessary to determine if oral NAC affects brain [GSH] and if so, to establish optimal dosage regimens to attain sustained elevation of brain [GSH] with repeated dosing.”
BackgroundTkáč, I., Öz, G., Adriany, G., Uǧurbil, K., & Rolf Gruetter, A. (2009) · Magnetic Resonance in Medicine · doi:10.1002/mrm.22086 · Cited by 366 · cited 2×
“Metabolite Quantification Metabolites were quantified using LCModel(21) as described before.(18,20) The metabolite model spectra were generated based on previously reported chemical shifts and coupling constants.”
MethodSelf-citationRegulation of Neuronal Glutathione Synthesis
Aoyama, K., Watabe, M., & Nakaki, T. (2008) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08r01cr · Cited by 364
Controlled trial of N-acetylcysteine for patients with probable Alzheimer’s disease
Adair, J. C., Knoefel, J. E., & Morgan, N. (2001) · Neurology · doi:10.1212/wnl.57.8.1515 · Cited by 240
Öz, G., & Tkáč, I. (2010) · Magnetic Resonance in Medicine · doi:10.1002/mrm.22708 · Cited by 203 · cited 2×
“Metabolite Quantification Metabolites were quantified using LCModel(21) as described before.(18,20) The metabolite model spectra were generated based on previously reported chemical shifts and coupling constants.”
MethodSelf-citationAssaf, Y., & Cohen, Y. (2000) · Magnetic Resonance in Medicine · doi:10.1002/(sici)1522-2594(200002)43:2 · Cited by 186
Emir, U. E., Tuite, P., & Öz, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030918 · Cited by 178
Self-citationExploring the link between glucocerebrosidase mutations and parkinsonism
Westbroek, W., Gustafson, A. M., & Sidransky, E. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.05.003 · Cited by 145 · cited 1×
“Altered GBA enzyme activity appears to contribute to increased α-synuclein misfolding and aggregation, which may also be enhanced by altered redox status within neurons.(9) Because GSH depletion in PD and an impaired adaptive response to oxidative stress in GD have both been observed, antioxidants that increase GSH ma…”
BackgroundRandomized, double‐blind, pilot evaluation of intravenous glutathione in Parkinson's disease
Hauser, R. A., Lyons, K. E., McClain, T., Carter, S., & Perlmutter, D. (2009) · Movement Disorders · doi:10.1002/mds.22401 · Cited by 143 · cited 1×
“Unfortunately, past PD research using intravenously administered GSH failed to provide a definitive benefit.(10) This failure may be related to a suboptimal dosing regimen but more likely is due to the saturable mechanism for GSH passage across the blood-brain barrier as well as a lack of uptake into neurons.”
N‐acetylcysteine prevents loss of dopaminergic neurons in the EAAC1−/− mouse
Berman, A., Chan, W., Brennan, A. M., Reyes, R. C., Adler, B. L., Suh, S. W., Kauppinen, T. M., Edling, Y., & Swanson, R. A. (2010) · Annals of Neurology · doi:10.1002/ana.22162 · Cited by 139
Mitochondrial alterations in Parkinson’s disease: new clues
Vila, M., Ramonet, D., & Perier, C. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05604.x · Cited by 131
Öz, G., Terpstra, M., Tkáč, I., Aia, P., Lowary, J., Tuite, P., & Rolf Gruetter, A. (2006) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20761 · Cited by 107
Self-citationRole ofN-acetylcysteine and cystine in glutathione synthesis in human erythrocytes
Whillier, S., Raftos, J. E., Chapman, B. E., & Kuchel, P. W. (2009) · Redox Report · doi:10.1179/135100009x392539 · Cited by 92
Sandhir, R., Sood, A., Mehrotra, A., & Kamboj, S. S. (2012) · Neurodegenerative Diseases · doi:10.1159/000334273 · Cited by 90
Hurd, R. W., Wilder, B. J., Helveston, W. R., & Uthman, B. M. (1996) · Neurology · doi:10.1212/wnl.47.5.1264 · Cited by 82 · cited 1×
“There are reports of positive effects of oral NAC in disorders with central nervous system involvement.(29,30) Future studies are necessary to determine if oral NAC affects brain [GSH] and if so, to establish optimal dosage regimens to attain sustained elevation of brain [GSH] with repeated dosing.”
BackgroundProteasomal dysfunction in sporadic Parkinson's disease
McNaught, K. S. P., Jackson, T., JnoBaptiste, R., Kapustin, A., & Olanow, C. W. (2006) · Neurology · doi:10.1212/wnl.66.10_suppl_4.s37 · Cited by 74
Quantitative assessment of cerebral blood volume by single-photon emission computed tomography.
Sabatini, U., Celsis, P., Viallard, G., Rascol, A., & Marc-Vergnes, J. P. (1991) · Stroke · doi:10.1161/01.str.22.3.324 · Cited by 54 · cited 1×
“However, blood makes up only approximately 3% of the volume in the brain.(26) Thus, the change detected in brain [GSH] in this study could not be due primarily to the contribution of blood GSH because the mean maximal increase in blood GSH of 30%measured in this study would only lead to an MRS voxel [GSH] increase of…”
BackgroundDeganuto, M., Pittis, M. G., Pines, A., Dominissini, S., Kelley, M. R., Garcia, R. C., Quadrifoglio, F., Bembi, B., & Tell, G. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21023 · Cited by 54
Changes in the Provision of Institutionalized Mental Health Care in Post-Communist Countries
Mundt, A. P., Frančišković, T., Gurovich, I., Heinz, A., Ignatyev, Y., Ismayilov, F., Kalapos, M. P., Krasnov, V. N., Mihai, A., Mir, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038490 · Cited by 53
Blood oxidative stress markers in Gaucher disease patients
Roversi, F. M., Galdieri, L. C., Grego, B. H. C., Souza, F. G., Micheletti, C., Martins, A. M., & D’Almeida, V. (2005) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.07.022 · Cited by 41
Cited by
Sorted by citations
Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
Oxidative Stress in Neurodegenerative Diseases
Simonian, N. A., & Coyle, J. T. (1996) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.36.040196.000503 · Cited by 1,377
Oxidative Stress in Neurodegenerative Diseases
Niedzielska, E., Smaga, I., Gawlik, M., Moniczewski, A., Stankowicz, P., Pera, J., & Filip, M. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9337-5 · Cited by 800
N-Acetylcysteine (NAC): Impacts on Human Health
Tenório, M. C. D. S., Graciliano, N. G., Moura, F. A., Oliveira, A. C. M. D., & Goulart, M. O. F. (2021) · Antioxidants · doi:10.3390/antiox10060967 · Cited by 526
Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review
Deepmala, Slattery, J., Kumar, N., Delhey, L., Berk, M., Dean, O., Spielholz, C., & Frye, R. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.04.015 · Cited by 463
Metadata
- Authors
- Holmay, M. J., Terpstra, M., Coles, L. D., Mishra, U., Ahlskog, M., Öz, G., Cloyd, J. C., & Tuite, P. J.
- Affiliations
- University of Minnesota (US)
- Cornell University (US)
- Corresponding author
- Holmay, Mary J.
- ORCID
- Venue
- Clinical Neuropharmacology
- Published
- 2013-07
- Volume
- 36
- Issue
- 4
- Pages
- 103-106
- ISSN
- 0362-5664 (ISSN-L)
- PMC
- PMC3934795
- OpenAlex
- W2010686114
- Cited by
- 216
- References
- 29
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 14 · 2023: 19 · 2022: 20 · 2021: 20 · 2020: 18 · 2019: 12 · 2018: 14 · 2017: 26 · 2016: 15 · 2015: 15 · 2014: 10 · 2013: 2
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (U54NS065768, P30NS076408)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015894)
- National Center for Research Resources (S10RR026783, P41RR008079)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Keywords
- N-acetylcysteine, glutathione, Parkinson's disease, Gaucher disease, brain glutathione, antioxidant therapy, redox state, neurodegenerative diseases
- MeSH terms
- Acetylcysteine, Adolescent, Antioxidants, Antiparkinson Agents, Brain, Female, Gaucher Disease, Glutathione, Humans, Infusions, Intravenous, Kinetics, Magnetic Resonance Imaging, Male, Middle Aged, Neurons, Oxidation-Reduction, Parkinson Disease, Up-Regulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
