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

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

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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  • Kynurenine and its metabolites, including kynurenic acid and quinolinic acid, have been implicated in mental health.

    “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

  • 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.

    “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).”
  • Kynurenines have been implicated in a range of neurobiological functions.

    “Other metabolites of tryptophan metabolism, kynurenines, have also been implicated in a range of neurobiological functions (392).”

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2 of the 215 references couldn’t be matched to a known paper.

Research works printed but not linked: 8

  1. [18]Copeland CS Neale SA Salt TE Soc. Neurosci. Abstr 2011 Vol. 36
  2. [73]Giorgini F Soc. Neurosci. Abstr 2011 Vol. 36
  3. [152]Alexander K Soc. Neurosci. Abstr 2011 Vol. 36
  4. [158]Justinova Z Soc. Neurosci. Abstr 2011 Vol. 36
  5. [161]Chapin DS Campbell B Strick CA Kozak R Soc. Neurosci. Abstr 2010 Vol. 35
  6. [162]Kozak R Soc. Neurosci. Abstr 2010 Vol. 35
  7. [163]Abbott A Soc. Neurosci. Abstr 2010 Vol. 35
  8. [164]Koshy Cherian A Soc. Neurosci. Abstr 2011 Vol. 36

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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
Venue
Nature Reviews Neuroscience
Published
2012-06-08
Volume
13
Issue
7
Pages
465-477
ISSN
  • 1471-003X (ISSN-L)
  • 1471-0048
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
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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