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Antioxidant and bioenergetic coupling between neurons and astrocytes
Abstract
Oxidative and nitrosative stress underlie the pathogenesis of a broad range of human diseases, in particular neurodegenerative disorders. Within the brain, neurons are the cells most vulnerable to excess reactive oxygen and nitrogen species; their survival relies on the antioxidant protection promoted by neighbouring astrocytes. However, neurons are also intrinsically equipped with a biochemical mechanism that links glucose metabolism to antioxidant defence. Neurons actively metabolize glucose through the pentose phosphate pathway, which maintains the antioxidant glutathione in its reduced state, hence exerting neuroprotection. This process is tightly controlled by a key glycolysis-promoting enzyme and is dependent on an appropriate supply of energy substrates from astrocytes. Thus brain bioenergetic and antioxidant defence is coupled between neurons and astrocytes. A better understanding of the regulation of this intercellular coupling should be important for identifying novel targets for future therapeutic interventions.
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“GSH levels have been shown to be lower in chronic schizophrenia, as measured in the CSF and post-mortem brain, and by MRS-based in vivo imaging 41,42 and the GSH system enzymes glutathione peroxidase (GPX) and glutathione reductase (GR) are also dysregulated 36 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [36]
In the citing paper
“Evidence for oxidative stress has been found in patients with schizophrenia, including increased lipid and protein oxidation in blood, cerebrospinal fluid (CSF) and post-mortem tissue 36,37 , as well as altered levels of plasma antioxidants (such as vitamins C and E, catalase, GSH and GSH-peroxidase) 36,38 and CSF superoxide dismutase-1 levels 39 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [36]
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Metadata
- Authors
- Fernandez-Fernandez, S., Almeida, A., & Bolaños, J. P.
- Affiliations
- Department of Biochemistry and Molecular Biology, Institute of Neurosciences of Castilla y León, University of Salamanca, Salamanca 37007, Spain
- Universidad de Salamanca (ES)
- ORCID
- Bolaños, Juan P.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2012-03-14
- Volume
- 443
- Issue
- 1
- Pages
- 3-11
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W2005896958
- Cited by
- 247
- References
- 161
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 19 · 2022: 20 · 2021: 20 · 2020: 25 · 2019: 12 · 2018: 18 · 2017: 17 · 2016: 20 · 2015: 26 · 2014: 19 · 2013: 24 · 2012: 7
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- astrocytes, neurons, oxidative stress, nitrosative stress, reactive oxygen species, reactive nitrogen species, pentose phosphate pathway, glutathione, glucose metabolism, bioenergetics, neuroprotection, neurodegenerative diseases, glycolysis
- MeSH terms
- Animals, Antioxidants, Astrocytes, Energy Metabolism, Glutathione, Humans, Neurons, Oxidation-Reduction, Oxidative Stress, Carbohydrate Metabolism
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