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.
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“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
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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
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“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…”
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“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.”
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“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.”
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Peethambaran, B., Leonce, C., & Patel, A. (2021) · International Journal of Complementary & Alternative Medicine · doi:10.15406/ijcam.2021.14.00528
Miloushev, V. Z., & Blasberg, R. G. (2017) · Springer eBooks · doi:10.1007/978-3-319-61401-4_9
Antioxidant Responses are Crucial for Defense against Misfolded Human Z-Type α1-Antitrypsin
Im, H., & Lim, J. (2022) · Protein and Peptide Letters · doi:10.2174/0929866529666220321151913
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Disorders of glutathione metabolism
Aoyama, K., Kinoshita, C., & Nakaki, T. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19041-4.00031-5
Muthmainah, M., Wiyono, N., Syah, F. K., Purnianto, A., Yudhani, R. D., & Wasita, B. (2025) · Journal of Taibah University Medical Sciences · doi:10.1016/j.jtumed.2025.05.004
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“Several studies have shown that interventions that enhance the p-Akt/Nrf2 pathway confer protection against oxidative stress in neurons, which strongly suggests that this pathway is a viable therapeutic target [13,14].”
Monti, D., Zabrecky, G. P., Kremens, D. E., Liang, T., Wintering, N., Vedaei, F., Navarreto, E., Gupta, M., Steinmetz, A., Bazzan, A. J., et al. (2026) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2026.108216
PET-MRI effects of N-acetylcysteine in patients with multiple sclerosis
Monti, D., Monadi, S. D., Mohamed, F. B., Alizadeh, M., Zabrecky, G. P., Wintering, N., Gupta, M., Steinmetz, A., Kremens, D. E., Bazzan, A. J., et al. (2026) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2026.08.014
“…of NAC has been shown to increase glutathione levels in both animal models (Vina et al., 1983; Martínez-Banaclocha et al., 1997) and human studies (Holmay et al., 2013), and reduce markers of oxidative damage in neurological conditions such as Parkinson ’ s disease (Martínez-Banaclocha et al.,…”
Dhanush, Y., Nizamuddin, N. D., Neelima, S., Kalpana, S., Arla, K. K., Ganesh, V. S., Sree, P. C., & Rohitha, C. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01961-2
“…synthesis, successfully increasing both blood and brain GSH levels in individuals with Parkinson’s disease, thereby restoring the critical antioxidant defence system that becomes depleted by 40–50% in the substantia nigra even before significant neuronal loss occurs (Holmay et al. 2013).”
Ghafari, B. M., Rajabi, A., Geramifar, P., Rahimi, A., karimimoghadam, H., Rahmani, K., & Rahimmi, A. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01991-w
“Brain GSH peaked about 30 min after the blood peak and remained elevated for at least 120 min, with a 55% increase in PD and a 34% increase in controls (Holmay et al. 2013 ).”
Glutathione in brain oxidative stress: from redox chemistry to clinical imaging
Aoyama, K. (2026) · Archives of Toxicology · doi:10.1007/s00204-026-04545-2
Neuroprotective therapies in Parkinson's disease
Atalah, H. N., Barakat, M., & Qansuwa, E. M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-54032-5.00005-x
Zhou, J. (2014) · University of Minnesota Digital Conservancy (University of Minnesota)
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
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