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Kynurenines in the mammalian brain: when physiology meets pathology
Open accessAbstract
The essential amino acid tryptophan is not only a precursor of serotonin but is also degraded to several other neuroactive compounds, including kynurenic acid, 3-hydroxykynurenine and quinolinic acid. The synthesis of these metabolites is regulated by an enzymatic cascade, known as the kynurenine pathway, that is tightly controlled by the immune system. Dysregulation of this pathway, resulting in hyper-or hypofunction of active metabolites, is associated with neurodegenerative and other neurological disorders, as well as with psychiatric diseases such as depression and schizophrenia. With recently developed pharmacological agents, it is now possible to restore metabolic equilibrium and envisage novel therapeutic interventions.
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“Kynurenine and its metabolites, including kynurenic acid and quinolinic acid, have been implicated in mental health (Cervenka et al., 2017;Schwarcz et al., 2012).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Schwarcz et al., 2012
In the citing paper
“Mounting evidence suggests that the GM modulates the tryptophan and kynurenine pathways and is a humoral route through which the GM may influence cognition at the level of the CNS (206–210).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [209]
In the citing paper
“Other metabolites of tryptophan metabolism, kynurenines, have also been implicated in a range of neurobiological functions (392).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [392]
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“In different regions of the forebrain, a modest increase in KYNA leads to a rapid decrease in extracellular Glu and dopamine levels, whereas inhibition of KYNA synthesis increases these neurotransmitter and acetylcholine levels [111].”
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“However, fluctuations in the systemic concentrations of these metabolites directly impacts KP metabolism in the CNS, including the synthesis of kynurenic acid and quinolinic acid in the brain [202].”
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Metadata
- Authors
- Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q.
- Affiliations
- University of Maryland, Baltimore (US)
- The Ohio State University (US)
- University of California, San Francisco (US)
- Corresponding author
- Schwarcz, Robert
- Venue
- Nature Reviews Neuroscience
- Published
- 2012-06-08
- Volume
- 13
- Issue
- 7
- Pages
- 465-477
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC3681811
- OpenAlex
- W2060050678
- Cited by
- 1,530
- References
- 215
- Citations by year
- 2026: 157 · 2025: 137 · 2024: 124 · 2023: 98 · 2022: 118 · 2021: 145 · 2020: 132 · 2019: 95 · 2018: 83 · 2017: 96 · 2016: 98 · 2015: 105 · 2014: 64 · 2013: 63 · 2012: 13
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH083729)
- National Institute of Neurological Disorders and Stroke (R01NS057715)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- kynurenine pathway, tryptophan metabolism, kynurenic acid, 3-hydroxykynurenine, quinolinic acid, neuroactive metabolites, neurodegenerative diseases, depression, schizophrenia, therapeutic targeting
- MeSH terms
- Animals, Brain, Humans, Kynurenine, Nervous System Diseases, Signal Transduction
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