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Role of Kynurenines in the Central and Peripherial Nervous Systems
Abstract
Kynurenine (KYN) is an intermediate in the pathway of the metabolism of tryptophan to nicotinic acid. KYN is formed in the mammalian brain (40%) and is taken up from the periphery (60%), indicating that it can be transported across the blood-brain barrier (BBB). In the brain, KYN can be converted to two other components of the pathway: the neurotoxic quinolinic acid (QUIN) and the neuroprotective kynurenic acid (KYNA). QUIN is probably the most widely studied metabolite of KYN, because it may cause excitotoxic neuronal cell loss and convulsions by interacting with the N-methyl-D-aspartate (NMDA) receptor complex, a type of glutamate receptor. KYNA is another metabolite of KYN; its synthesis is catalysed by KYN aminotransferases. This is the only known endogenous NMDA receptor inhibitor, which can act at the glycine site on the receptor complex. Furthermore, KYNA non-competitively inhibits alpha7 nicotinic acetylcholine presynaptic receptors (nAChRs), inhibiting glutamate release, and regulates the expression of alpha4beta2 nAChR. It is well-known that the activation of excitatory amino acid (EAA) receptors can play a role in a number of neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, stroke and epilepsy. Various studies have been made of whether the EAA receptor antagonist KYNA can exert a therapeutic effect in these neurological disorders. It has been established that KYNA has only a very limited ability to cross the BBB. Other KYNA derivatives have been synthesised (e.g. glucosamine-KYNA, 4-chloro-KYNA and 7-chloro-KYNA), which are well transported across the BBB and act on the glutamate receptors. Moreover, it has been demonstrated that probenecid, a known inhibitor of the transport of organic acids (e.g. KYNA), increases the cerebral concentration of KYNA. There is another new perspective to the maintenance of a high level of KYNA in the brain: the use of enzyme inhibitors, which can block the synthesis of the neurotoxic QUIN. These are some of the most promising possibilities as novel therapeutic strategies for the treatment of neurodegenerative diseases, in which the hyperactivation of amino acid receptors could be involved. The presence and importance of KYN derivatives in the periphery are also discussed in the light of recent publications.
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“While peripheral kynurenic acid mostly does not cross the blood-brain-barrier (Nemeth et al., 2005)”
From Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naïve patients with major depressive disorder: An exploratory pilot case-control study (2018) · cites this paper as Nemeth et al., 2005
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Items 101–169 of 169
Maciejak, P., Szyndler, J., Turzyńska, D., et al. (2008) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2008.10.010 · Cited by 17
Love, A. C., Schwartz, I. S., & Petzke, M. M. (2014) · Journal of Leukocyte Biology · doi:10.1189/jlb.4a0714-339r · Cited by 17
“Kynurenines, including modified metabolites, such as 3-hydroxylkynurenine and anthranilic acid, can be directly cytotoxic to cells through the generation of free radicals, lipid peroxidation, and oxidative stress, leading to cellular apoptosis [72–74].”
BackgroundMitsuhashi, S., Fukushima, T., Arai, K., Tomiya, M., Santa, T., Imai, K., & Toyo’oka, T. (2007) · Analytica Chimica Acta · doi:10.1016/j.aca.2007.01.033 · Cited by 16
Tryptophan Metabolism in Obesity: The Indoleamine 2,3-Dioxygenase-1 Activity and Therapeutic Options
Engin, A. B., & Engin, A. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-63657-8_21 · Cited by 15
Kamishikiryo, T., Okada, G., Itai, E., Masuda, Y., Yokoyama, S., Takamura, M., Fuchikami, M., Yoshino, A., Mawatari, K., Numata, S., et al. (2022) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13373 · Cited by 15
SNAP and SIN-1 increase brain production of kynurenic acid
Luchowski, P., & Urbańska, E. M. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.02.044 · Cited by 15
Polycystic Ovary Syndrome Pathophysiology: Integrating Systemic, CNS and Circadian Processes
Anderson, G. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2901024 · Cited by 16
“Notably, over 60% of brain kynurenine is derived from the periphery [93], indicating that adipocyte-derived kynurenine may be a significant contributor to aryl hydrocarbon receptor (AhR)-driven changes in the brain, including the hypothalamic paraventricular nucleus (PVN), thereby allowing…”
BackgroundAbo, M., Yamauchi, H., Suzuki, M., et al. (2006) · Neurosignals · doi:10.1159/000094876 · Cited by 14
“In addition, kynurenic acid non-competitively inhibits release of glutamate by acting on nicotinic acetylcholine presynaptic receptors [”
BackgroundKYNA Derivatives with Modified Skeleton; Hydroxyquinolines with Potential Neuroprotective Effect
Lőrinczi, B., & Szatmári, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111935 · Cited by 13
“Abbreviations Acetonitrile MeCN Blood-brain barrier BBB 1,2-Dichlorobenzene DCB Diethylacetylene dicarboxylate DEAD Diethyl fumarate DEF N,N′-Diisopropylcarbodiimide DIC Dimethylacetylene dicarboxylate DMAD N,N-Dimethylformamide DMF Diphenyl ether Ph2O 1,3-Bis(diphenylphosphino)propane dppp Electron-donating groups ED…”
BackgroundAssociation between small intestine bacterial overgrowth and psychiatric disorders
Bogielski, B., Michalczyk, K., Głodek, P., Tempka, B., Gębski, W., & Stygar, D. M. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1438066 · Cited by 14
“On the other hand, quinolinic acid, the other product of the KYN pathway, acts as an NMDA receptor agonist that presents neurotoxic effects and enhances free radical production (49).”
BackgroundROSZKOWICZ-OSTROWSKA, K. I., Młotkowska, P., Kowalczyk, P., Marciniak, E., Barszcz, M., & Misztal, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010136 · Cited by 13
Zakrocka, I. N., Kocki, T., & Turski, W. A. (2017) · Pharmacological Reports · doi:10.1016/j.pharep.2017.01.023 · Cited by 13
Lőrinczi, B., Csámpai, A., Fülöp, F., et al. (2020) · RSC Advances · doi:10.1039/d0ra08325a · Cited by 12
Electrochemical Detection of Tryptophan Metabolites via Kynurenine Pathway by Using Nanocarbon Films
Kato, D., Kamata, T., & Sumimoto, M. (2021) · Electroanalysis · doi:10.1002/elan.202100241 · Cited by 11
Ishii, K., Iizuka, H., Ogaya, T., Song, Z., & Fukushima, T. (2011) · Chirality · doi:10.1002/chir.20938 · Cited by 11
Plasma Kynurenic Acid Concentration in Patients Undergoing Cardiac Surgery: Effect of Anaesthesia
Kotlińska-Hasiec, E., Nowicka-Stążka, P., Parada-Turska, J., Stążka, K., Stążka, J., Zadora, P., & Dąbrowski, W. (2014) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-014-0312-z · Cited by 11
Zakrocka, I. N., Turski, W. A., & Kocki, T. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.07.023 · Cited by 11
Ciapała, K., Pawlik, K., Ciechanowska, A., Mika, J., & Rojewska, E. (2023) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2023.116382 · Cited by 10
Endogenous Kynurenic Acid and Neurotoxicity
Urbańska, E. M., Chmiel-Perzyńska, I., Perzyński, A., Derkacz, M., & Owe‐Larsson, B. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_92 · Cited by 13
Kynurenines and Inflammation: A Remarkable Axis for Multiple Sclerosis Treatment
Carrillo‐Mora, P., Landa‐Solís, C., Valle‐García, D., Luna‐Angulo, A. B., Avilés‐Arnaut, H., Robles-Bañuelos, B., Sánchez‐Chapul, L., & Rangel‐López, E. (2024) · Pharmaceuticals · doi:10.3390/ph17080983 · Cited by 9
Huang, J., Zhang, P., Zhou, Y., Tong, J., Cui, Y., Tan, S., Wang, Z., Yang, F., Kochunov, P., Tian, B., et al. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.11.002 · Cited by 9
Endogenous Kynurenic Acid and Neurotoxicity
Urbańska, E. M., Chmiel-Perzyńska, I., Perzyński, A., Derkacz, M., & Owe‐Larsson, B. (2021) · Springer eBooks · doi:10.1007/978-3-030-71519-9_92-1 · Cited by 9
Depression, Inflammation and Tryptophan Metabolism
McCusker, R. H., Kavelaars, A., Heijnen, C. J., Dantzer, R., & Kelley, K. W. (2013) · Wiley eBooks · doi:10.1002/9781118314814.ch23 · Cited by 9
Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain
Notartomaso, S., Boccella, S., Antenucci, N., Ricciardi, F., Fazio, F., Liberatore, F., Scarselli, P., Scioli, M., Mascio, G., Bruno, V., et al. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.892870 · Cited by 8
Liu, J.-C., Yu, H., Li, R., Zhou, C., Shi, Q., Guo, L. Q., & He, H. (2023) · Medicina · doi:10.3390/medicina59020413 · Cited by 10
“QUIN is considered a neurotoxic metabolite that participates in the generation of ROS and stimulates synaptosomal glutamate release [25], whereas PIC is considered a neuroprotective metabolite that exhibits immunomodulatory properties [26].”
BackgroundInvestigational Microbiological Therapy for Glioma
Wang, J., Liu, Y., Zhang, A., Yu, W., Lei, Q., Xiao, B., & Luo, Z. (2022) · Cancers · doi:10.3390/cancers14235977 · Cited by 7
Iizuka, H., Watanabe, S., Koshikawa, M., et al. (2013) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-013-7010-2 · Cited by 7
“On the other hand, L-tryptophan (L-Trp), one of the essential amino acids, is metabolized to several neuroactive metabolites such as quinolinic acid (QA), kynurenic acid (KYNA), and serotonin by two metabolic pathways, namely, the kynurenine and serotonin pathways [2, 3].”
BackgroundKynurenine Pathway after Kidney Transplantation: Friend or Foe?
Zakrocka, I. N., Urbańska, E. M., Załuska, W., & Kronbichler, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25189940 · Cited by 5
Quinolinic acid-immunoreactivity in the naïve mouse brain
Lopez, Y. P., Kenis, G., Rutten, B. P. F., Myint, A.-M., Steinbusch, H. W. M., & van den Hove, D. (2015) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2015.10.010 · Cited by 6
Chojnacki, M., Błońska, A., Kaczka, A., Chojnacki, J., Walecka‐Kapica, E., Romanowska, N., Przybyłowska-Sygut, K., & Popławski, T. (2025) · Nutrients · doi:10.3390/nu17132232 · Cited by 5
“Subsequently, the “tryptophan-kynurenine enhancement hypothesis” has been proposed to explain the mechanism of central fatigue [57,58].”
Benign infantile seizures followed by autistic regression in a boy with 16p11.2 deletion
Milone, R., Valetto, A., Bertini, V., & Sicca, F. (2017) · Epileptic Disorders · doi:10.1684/epd.2017.0909 · Cited by 6
Clenbuterol enhances the production of kynurenic acid in brain cortical slices and glial cultures.
Luchowska, E., Kloc, R., Wnuk, S., et al. (2009) · PubMed · Cited by 5
Qi, H., Chi, X., Zhang, W., Song, H., Wang, Y., Liu, Z., Wang, H., & Xu, B. (2024) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2024.175931 · Cited by 5
Farup, P. G., & Hestad, K. A. (2022) · Applied Sciences · doi:10.3390/app12052648 · Cited by 4
“Trypt and Kyn easily pass the blood–brain barrier, and 60–80% of Kyn in the brain is of exogenous origin [1,33].”
BackgroundCarotid surgery affects plasma kynurenic acid concentration: A pilot study
Dąbrowski, W. (2014) · Medical Science Monitor · doi:10.12659/msm.890212 · Cited by 4
Tomiya, M., Fukushima, T., Ogaya, T., Sone, Y., Mitsuhashi, S., & Toyo’oka, T. (2009) · Biomedical Chromatography · doi:10.1002/bmc.1336 · Cited by 4
Sthoeger, Z. M., Sharabi, A., Zinger, H., Asher, I., & Mozes, E. (2018) · Clinical Immunology · doi:10.1016/j.clim.2018.08.012 · Cited by 3
Korimová, A., Čı́žková, D., Toldi, J., et al. (2012) · Open Life Sciences · doi:10.2478/s11535-012-0096-2 · Cited by 3
Self-citationWu, Y., Srirajavatsavai, V., Monplaisir, K. M., Sambanthamurthi, R., & Gupta, S. V. (2015) · The FASEB Journal · doi:10.1096/fasebj.29.1_supplement.271.8 · Cited by 3
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Smith, Q. R., & Lockman, P. R. (2010) · Methods and principles in medicinal chemistry · doi:10.1002/9783527633166.ch11 · Cited by 3
Microbiota-related metabolites correlated with the severity of COVID-19 patients
Wang, X., Wang, J.-Y., Yu, F., Shi, D., Xie, J., Li, L., & Wang, B. (2024) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2024.12.006 · Cited by 2
Zheng, Y., Hong, D., Yuan, J., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-94311-8 · Cited by 2
“Its precursor, kynurenic acid, plays pivotal roles in brain function and is linked to conditions such as schizophrenia and neurodegenerative disorders 67 .”
Chettupalli, A. K., Bukke, S. P. N., Rahaman, S. A., Bodige, M., Kanakaraju, V. K., Kavitha, M., Srinivasarao, D., Mohammed, A., Goruntla, N., & Yadesa, T. M. (2025) · BMC Biotechnology · doi:10.1186/s12896-025-01069-y · Cited by 3
Towards Automated Testing of Kynurenine for Point-of-Care Metabolomics
Bhattacharyya, D., LeVatte, M., & Wishart, D. S. (2025) · Methods and Protocols · doi:10.3390/mps8030056 · Cited by 2
Xu, J., Wei, L., Fu, J., Kong, Z., & Cai, L. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47090764 · Cited by 2
The guide through brain-gut-enteric microbiota axis - regulation pathways and related disorders
Kolasińska, K., Kwiatkowski, S., Knap, B., Czerwiński, G., Poniewierka, E., & Waszczuk, E. (2018) · World Scientific News · Cited by 2
Sasaki, T., Fukushima, T., Yamashita, K., & Toyo’oka, T. (2009) · Chirality · doi:10.1002/chir.20737 · Cited by 2
Lopatina, N. G., Зачепило, Т. Г., Chesnokova, E. G., et al. (2011) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-011-9465-y · Cited by 2
Kinureninek és gyógyszerkutatás
Tóth, F., Fülöp, F., Szatmári, I., Toldi, J., Dékány, I., & Vécsei, L. (2020) · Orvosi Hetilap · doi:10.1556/650.2020.31673 · Cited by 2
Self-citationBroken Connections: The Evidence for Neuroglial Failure in ME/CFSPreprint
Renz‐Polster, H. (2021) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/ef3n4 · Cited by 1
Kinureninek elektrofiziológiai hatásvizsgálata
Rózsa, É. (2008) · SZTE Repository of Dissertations (University of Szeged)
Developmental and psychoneuroimmunological mechanisms in depression
Pujol-Lopez, Y. (2015) · Research Publications (Maastricht University) · doi:10.26481/dis.20151030yp
The Toll of too much Interferon
Maria, N. I. (2015) · RePub (Erasmus University Rotterdam)
Gyógyszertranszporterek szerepe a központi idegrendszerben
Erdő, F., Temesszentandrási‐Ambrus, C., & Beéry, E. (2016) · Orvosi Hetilap · doi:10.1556/650.2016.30382
A kinureninrendszer és a stressz
Majláth, Z., & Vécsei, L. (2015) · Orvosi Hetilap · doi:10.1556/650.2015.30246
Self-citationGárdián, G., Sas, K., Toldi, J., & Vécsei, L. (2009) · doi:10.1093/acprof:oso/9780195326697.003.0018
Self-citationZmarowski, A. (2008) · OhioLink ETD Center (Ohio Library and Information Network)
A novel animal model for testing the in vivo potency of putative local anesthetic compounds
Sáfrány-Fárk, Á. (2019) · SZTE Repository of Dissertations (University of Szeged) · doi:10.14232/phd.10169
“It is synthesized in the central nervous system, including the spinal cord, predominantly by glial cells and it is found in low concentrations (10150 nM) both centrally and peripherally (Bohar et al., 2015; Moroni et al., 1988; Nemeth et al., 2005; Pawlak et al., 2000; Schwarcz et al., 2002; Turski et al., 1988; Urban…”
BackgroundKamishikiryo, T., Okada, G., Itai, E., Masuda, Y., Yokoyama, S., Takamura, M., Fuchikami, M., Yoshino, A., Mawatari, K., Numata, S., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-911537/v1
Neurochemistry of Endogenous Antinociception
Horváth, G. (2010) · Advances in neurobiology · doi:10.1007/978-1-4419-7104-3_15
“Thus, direct support for its physiological role in glutamatergic and cholinergic neurotransmission has been reported (Carpenedo et al., 2001; Nemeth et al., 2005; Schwarcz and Pellicciari, 2002).”
Background(2012) · Wiley eBooks · doi:10.1002/9781118357514.biblio
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Schütz, B., & Crecelius, M. (2023) · Zeitschrift für Orthomolekulare Medizin · doi:10.1055/a-2009-3541
Ma, P.-J., Man, Y., Shen, F.-Q., Li, M., Wang, H., Ren, F.-L., Ye, J.-Y., Pan, Y. P., & Wang, Y. (2026) · Comprehensive physiology · doi:10.1002/cph4.70207 · Cited by 1
“More than 60% of KYN is transported directly from the peripheral circulation to the brain, where it is converted into other neuroactive compounds (Németh et al. 2005; Platten et al. 2019).”
Dietary Tryptophan Requirements in Adults Aged >60 Years Is Not Affected by Sex or Decades of Age
Wang, Z., Tomlinson, C., Pencharz, P. B., Li, B., Kong, D., Elango, R., & Courtney‐Martin, G. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101827
Thioperamide, antagonist of histamine H3 receptors, increases brain production of kynurenic acid
Jarosławska-Zych, A., Kowalczyk, M., Kloc, R., et al. (2010) · Journal of Pre-Clinical and Clinical Research
Metadata
- Authors
- Nemeth, H., Toldi, J., & Vecsei, L.
- Venue
- Current Neurovascular Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2005-07-01
- Volume
- 2
- Issue
- 3
- Pages
- 249-260
- ISSN
- 1567-2026 (ISSN-L)
- OpenAlex
- W2111737222
- Cited by
- 169
- References
- 0
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 7 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 9 · 2012: 7
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Neurovascular Research (publishedVersion)
- PubMed (publishedVersion)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- kynurenine, tryptophan metabolism, kynurenic acid, quinolinic acid, NMDA receptor, alpha7 nicotinic acetylcholine receptor, blood-brain barrier, excitotoxicity, neurodegenerative diseases, probenecid, kynurenine derivatives, glutamate receptors, neuroprotection, epilepsy, Parkinson's disease
- MeSH terms
- Animals, Central Nervous System, Humans, Kynurenine, Nervous System Diseases, Peripheral Nervous System
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