Metabolism and functions of glutathione in brain
Abstract
The tripeptide glutathione is the thiol compound present in the highest concentration in cells of all organs. Glutathione has many physiological functions including its involvement in the defense against reactive oxygen species. The cells of the human brain consume about 20% of the oxygen utilized by the body but constitute only 2% of the body weight. Consequently, reactive oxygen species which are continuously generated during oxidative metabolism will be generated in high rates within the brain. Therefore, the detoxification of reactive oxygen species is an essential task within the brain and the involvement of the antioxidant glutathione in such processes is very important. The main focus of this review article will be recent results on glutathione metabolism of different brain cell types in culture. The glutathione content of brain cells depends strongly on the availability of precursors for glutathione. Different types of brain cells prefer different extracellular glutathione precursors. Glutathione is involved in the disposal of peroxides by brain cells and in the protection against reactive oxygen species. In coculture astroglial cells protect other neural cell types against the toxicity of various compounds. One mechanism for this interaction is the supply by astroglial cells of glutathione precursors to neighboring cells. Recent results confirm the prominent role of astrocytes in glutathione metabolism and the defense against reactive oxygen species in brain. These results also suggest an involvement of a compromised astroglial glutathione system in the oxidative stress reported for neurological disorders.
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Improvement of microcirculation and penumbral tissue oxygenation mediated by Mexidol and Semax may be crucial to reverse the HIF-1α-dependent blockade of PGC-1α expression.
“Improvement of microcirculation and penumbral tissue oxygenation mediated by the drugs Mexidol and Semax may be crucial to reverse the HIF-1α-dependent blockade of PGC-1α expression [14,86,87].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [86]
HIF-1α is a key factor in suppressing mitochondrial biogenesis and PGC-1α expression through negative regulation of MYC and MYC-dependent transcription factors (PPARs and ERRs) that activate the PGC-1α gene.
“HIF-1α is also a key factor in suppressing mitochondrial biogenesis and PGC-1α expression through mechanisms of negative regulation of the transcription factor MYC and the MYC-dependent transcription factors (PPARs and ERRs) that activate the PGC-1α gene [14,86,87].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [86]
GSH is present in brain cells in millimolar concentrations.
“In the brain, millimolar concentrations of GSH are present within the cells (Dringen 2000), while extracellular GSH concentrations in the brain are orders of magnitude lower (Hilgier et al. 2010; Orwar et al. 1994).”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Dringen 2000
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“Improvement of microcirculation and penumbral tissue oxygenation mediated by the drugs Mexidol and Semax may be crucial to reverse the HIF-1α-dependent blockade of PGC-1α expression [14,86,87].”
BackgroundBrain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease
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- Authors
- Dringen, R.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Dringen, Ralf
- ORCID
- Dringen, Ralf
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 62
- Issue
- 6
- Pages
- 649-671
- ISSN
- 0301-0082 (ISSN-L)
- OpenAlex
- W2169714384
- Cited by
- 1,702
- References
- 5
- Citations by year
- 2026: 42 · 2025: 52 · 2024: 48 · 2023: 59 · 2022: 60 · 2021: 71 · 2020: 82 · 2019: 48 · 2018: 78 · 2017: 108 · 2016: 76 · 2015: 97 · 2014: 111 · 2013: 91 · 2012: 102
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- glutathione, glutathione metabolism, brain, reactive oxygen species, oxidative stress, antioxidant defense, glutathione precursor, astrocytes, peroxide detoxification, neurological disorders
- MeSH terms
- Animals, Astrocytes, Biological Transport, Brain, Cell Communication, Cells, Cultured, Extracellular Space, Glutathione, Humans, Neurons, Oligodendroglia, Oxidation-Reduction, Reactive Oxygen Species, Microglia, Neurodegenerative Diseases
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