What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics?
Open accessAbstract
The kynurenine pathway has received increasing attention as its connection to inflammation, the immune system and neurological conditions has become more apparent. It is the primary route for tryptophan catabolism in the liver and the starting point for the synthesis of nicotinamide adenine dinucleotide in mammals. Dysregulation or overactivation of this pathway can lead to immune system activation and accumulation of potentially neurotoxic compounds. These aspects make the kynurenine pathway a promising target for therapeutic development to treat inflammation and disease with neurological aspects, especially in cancer patients undergoing chemotherapy.
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Quinolinic acid is an excitotoxin with high affinity for glutamate N-methyl-d-aspartate (NMDA) receptors.
“which is an excitotoxin with high affinity for glutamate N-methyl-d-aspartate (NMDA) receptors186.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [186]
Because TLR3 is abundantly expressed in the brain, abnormal activation of NMDA receptor signalling by quinolinic acid might be at least partially responsible for numerous neurological diseases.
“As TLR3 is abundantly expressed in the brain187, abnormal activation of NMDA receptor signalling by quinolinic acid might be at least partially responsible for numerous neurological diseases186,188.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [186]
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Cites
Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530 · see citing works
Endogenous kynurenines as targets for drug discovery and development
Stone, T. W., & Darlington, L. G. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd870 · Cited by 768 · see citing works
Lapin, I. P., & Oxenkrug, G. F. (1969) · The Lancet · doi:10.1016/s0140-6736(69)91140-4 · Cited by 710 · see citing works
Depressive disorders and immunity: 20 years of progress and discovery
Irwin, M. R., & Miller, A. H. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.01.010 · Cited by 676 · see citing works
Raison, C. L., Dantzer, R., Kelley, K. W., Lawson, M. A., Woolwine, B. J., Vogt, G., Spivey, J. R., Saito, K., & Miller, A. H. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.116 · Cited by 630 · see citing works
The kynurenine system and immunoregulation
Mándi, Y., & Vécsei, L. (2012) · Journal of neural transmission · doi:10.1007/s00702-011-0681-y · Cited by 382 · see citing works
An expanding range of targets for kynurenine metabolites of tryptophan
Stone, T. W., Stoy, N. S., & Darlington, L. G. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.09.006 · Cited by 344 · see citing works
Beal, M. F., Matson, W. R., Swartz, K. J., Gamache, P. H., & Bird, E. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb03143.x · Cited by 312 · see citing works
The kynurenine pathway of tryptophan degradation as a drug target
Schwarcz, R. (2004) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2003.10.006 · Cited by 265 · see citing works
The Physiological Action of Picolinic Acid in the Human Brain
Grant, R., Coggan, S. E., & Smythe, G. A. (2009) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s2469 · Cited by 219 · see citing works
Tryptophan Nutrition and Metabolism: An Overview
Peters, J. C. (1991) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5952-4_32 · Cited by 212 · see citing works
de la Cruz, V. P., Carrillo-Mora, P. U., & Santamarı́a, A. (2012) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s8158 · Cited by 193 · see citing works
Ring-Cleaving Dioxygenases with a Cupin Fold
Fetzner, S. (2012) · Applied and Environmental Microbiology · doi:10.1128/aem.07651-11 · Cited by 191 · see citing works
Tryptophan Metabolites and Brain Disorders
Stone, T. W., Mackay, G. M., Forrest, C., Clark, C. J., & Darlington, L. (2003) · Clinical Chemistry and Laboratory Medicine · doi:10.1515/cclm.2003.129 · Cited by 181 · see citing works
Zhang, Y., Colabroy, K. L., Begley, T. P., & Ealick, S. E. (2005) · Biochemistry · doi:10.1021/bi047353l · Cited by 106 · see citing works
Tryptophan Catabolism: Identification and Characterization of a New Degradative Pathway
Colabroy, K. L., & Begley, T. P. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.22.7866-7869.2005 · Cited by 87 · see citing works
Miller, A. H. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.140 · Cited by 76 · see citing works
Heme-dependent dioxygenases in tryptophan oxidation.
Geng, J., & Liu, A.-M. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2013.11.009 · Cited by 52 · see citing works
Self-citationDo cytokines really sing the blues?
Raison, C. L., & Miller, A. H. (2013) · Europe PMC (PubMed Central) · Cited by 52 · see citing works
My life with tryptophan—Never a dull moment
Hayaishi, O. (1993) · Protein Science · doi:10.1002/pro.5560020320 · Cited by 46 · see citing works
Huo, L., Liu, F., Iwaki, H., et al. (2014) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24722 · Cited by 29 · see citing works
Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action
Huo, L., Davis, I., Liu, F., et al. (2015) · Nature Communications · doi:10.1038/ncomms6935 · Cited by 28 · see citing works
Self-citationHuo, L., Davis, I., Chen, L., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.496869 · Cited by 22 · see citing works
Self-citationGenentech dives deeper into the next wave of cancer immunotherapies
Crunkhorn, S. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4502 · Cited by 15 · see citing works
Huo, L., & Liu, A. (2012) · Worldwide Protein Data Bank · doi:10.2210/pdb4ih3/pdb · Cited by 3 · see citing works
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- Authors
- Davis, I., & Liu, A.
- Affiliations
- Georgia State University (US)
- Corresponding author
- Liu, Aimin
- ORCID
- Venue
- Expert Review of Neurotherapeutics
- Publisher
- Informa UK Limited
- Published
- 2015-05-24
- Volume
- 15
- Issue
- 7
- Pages
- 719-721
- ISSN
- 1473-7175 (ISSN-L)
- 1744-8360
- PMC
- PMC4482796
- OpenAlex
- W1867264094
- Cited by
- 200
- References
- 25
- Citations by year
- 2026: 11 · 2025: 27 · 2024: 24 · 2023: 33 · 2022: 27 · 2021: 25 · 2020: 9 · 2019: 21 · 2018: 12 · 2017: 7 · 2016: 4
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Expert Review of Neurotherapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM107529, GM108988, R01GM107529, R01GM108988)
- 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 catabolism, kynurenine, neuroinflammation, immune activation, NAD biosynthesis, neurotherapeutics, chemotherapy-induced neurotoxicity, cancer patients
- MeSH terms
- Animals, Humans, Kynurenine, Nervous System Diseases, Tryptophan, Signal Transduction
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