The Glutathione System in Parkinson’s Disease and Its Progression
Open accessAbstract
Redox dysfunctions and neuro-oxidative stress play a major role in the pathophysiology and progression of Parkinson's disease (PD). Glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio are lowered in oxidative stress conditions and may lead to increased oxidative toxicity. GSH is involved not only in neuro-immune and neuro-oxidative processes, including thiol redox signaling, but also in cell proliferation and differentiation and in the regulation of cell death, including apoptotic pathways. Lowered GSH metabolism and a low GSH/GSSG ratio following oxidative stress are associated with mitochondrial dysfunctions and constitute a critical factor in the neuroinflammatory and neurodegenerative processes accompanying PD. This review provides indirect evidence that GSH redox signaling is associated with the pathophysiology of PD. Nevertheless, it has not been delineated whether GSH redox imbalances are a causative factor in PD or whether PD-associated pathways cause the GSH redox imbalances in PD. The results show that antioxidant approaches, including neuroprotective and anti-neuroinflammatory agents, which neutralize reactive oxygen species, may have therapeutic efficacy in the treatment of PD and its progression.
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Oxidative stress and alterations in the GSH metabolism of the brain have been connected with many neurological and neurodegenerative diseases.
“Oxidative stress and alterations in the GSH metabolism of the brain have been connected with many neurological and neurodegenerative diseases as recently summarized (Asanuma and Miyazaki 2021; Bell et al. 2024; Bjørklund et al. 2021, 2020; Bottino et al. 2021; Iskusnykh et al. 2022; Kim 2021; Murray et al. 2024).”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Bjørklund et al. 2021
GSH depletion starts before other PD symptoms, including diminished complex I activity and development of Lewy bodies, and relates with disease severity.
“Although GSH is not the sole antioxidant involved in PD, it seems to relate with disease severity because GSH depletion starts before other PD symptoms, including diminished complex I activity in the mitochondria and the development of Lewy bodies [42,43].”
From Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease (2022) · cites this paper as [42]
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One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration
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Glutathione Metabolism of the Brain—The Role of Astrocytes
Dringen, R., & Arend, C. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70073 · Cited by 46 · see citing works
- Authors
- Bjørklund, G., Peana, M., Maes, M., Dadar, M., & Severin, B.
- Affiliations
- Council for Nutritional and Environmental Medicine (NO)
- University of Sassari (IT)
- Deakin University (AU)
- Razi Vaccine and Serum Research Institute (IR)
- Ovidius University (RO)
- Corresponding author
- Bjørklund, Geir
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 120
- Pages
- 470-478
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W3093319781
- Cited by
- 186
- References
- 143
- Citations by year
- 2026: 16 · 2025: 40 · 2024: 42 · 2023: 44 · 2022: 34 · 2021: 9 · 2020: 1
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- Parkinson's disease, glutathione, GSH/GSSG ratio, oxidative stress, redox signaling, mitochondrial dysfunction, neuroinflammation, neurodegeneration, apoptosis, reactive oxygen species, antioxidant therapy, neuroprotection
- MeSH terms
- Antioxidants, Glutathione, Humans, Oxidation-Reduction, Parkinson Disease, Oxidative Stress
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