Cited by 1,530Tryptophan and brain disordersAmino Acid Enzymes and MetabolismNeuroinflammation and Neurodegeneration Mechanisms

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Kynurenines in the mammalian brain: when physiology meets pathology

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Schwarcz, Robert, Bruno, John P., Muchowski, Paul J., Wu, Hui-Qiu·2012·Nature Reviews Neuroscience

DOI 10.1038/nrn3257PMC PMC3681811

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Abstract

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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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
ORCID: Schwarcz, Robert
Bruno, John P.
Wu, Hui-Qiu
Venue: Nature Reviews Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2012-06-08
Volume: 13
Issue: 7
Pages: 465-477
ISSN: 1471-003X (ISSN-L)
1471-0048
DOI: 10.1038/nrn3257
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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Kynurenines in the mammalian brain: when physiology meets pathology

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