Role of Kynurenines in the Central and Peripherial Nervous Systems

Nemeth, Hajnalka; Toldi, Jozsef; Vecsei, Laszlo

doi:10.2174/1567202054368326

Cited by 169Tryptophan and brain disordersAmino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology Research

Role of Kynurenines in the Central and Peripherial Nervous Systems

Nemeth, Hajnalka, Toldi, Jozsef, Vecsei, Laszlo·2005·Current Neurovascular Research

DOI 10.2174/1567202054368326

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.2174/1567202054368326

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Peripheral kynurenic acid mostly does not cross the blood-brain barrier.
“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

Sorted by citations

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice
O'Connor, J. C., Lawson, M. A., André, C., Moreau, M., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002148 · Cited by 1,278 · see citing works
A Meta-Analysis of Cytokines in Alzheimer's Disease
Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., & Herrmann, N. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.012 · Cited by 1,108 · see citing works
The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat
Desbonnet, L., Garrett, L., Clarke, G., Bienenstock, J., & Dinan, T. G. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.03.009 · Cited by 952 · see citing works
“However, kynurenic acid (KA), which is also produced from kynurenine by an alternative pathway, possesses neuroprotective properties, as it acts as an antagonist at the NMDA receptor (Németh et al., 2005).”
Background
Tryptophan metabolism in the central nervous system: medical implications
Ruddick, J. P., Evans, A. K., Nutt, D. J., Lightman, S. L., Rook, G. A. W., & Lowry, C. A. (2006) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399406000068 · Cited by 519 · see citing works
Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders
Sas, K., Robotka, H., Toldi, J., & Vécsei, L. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.033 · Cited by 465 · see citing works
“In some neurodegenerative diseases or other pathological states, the changes in the KYN pathway metabolites are modest and balanced with regard to the two KYN branches, probably depending on whether astrocytes or microglia cells are preferentially taking part in the process (reviewed by [101,102,124,125]).”
BackgroundSelf-citation
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
Self-citation
Systemic infection, inflammation and acute ischemic stroke
McColl, B. W., Allan, S. M., & Rothwell, N. J. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.08.019 · Cited by 319 · see citing works
Structure, expression, and function of kynurenine aminotransferases in human and rodent brains
Han, Q., Cai, T., Tagle, D. A., & Li, J. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0166-4 · Cited by 240 · see citing works
Cell signaling and neuronal death.
Hara, M. R., & Snyder, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105311 · Cited by 232 · see citing works
Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms
Su, F., Bai, F., & Zhang, Z. (2016) · Neuroscience Bulletin · doi:10.1007/s12264-016-0055-4 · Cited by 221 · see citing works
“Moreover, indoleamine 2, 3-dioxygenase, which is activated by cytokines, may be an additional candidate mechanism of cytokineinduced AD pathology and could lead to increased levels of the neurotoxic factor, quinolinic acid [138], and promote tau hyperphosphorylation [139].”
Background
Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's disease
Schwarcz, R. M., Guidetti, P., Sathyasaikumar, K. V., & Muchowski, P. J. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.04.005 · Cited by 175 · see citing works
“Almost without exception, the usefulness of the new synthetic compounds for the study of brain KP metabolism in vivo is restricted by their difficulty to cross the blood–brain barrier after systemic administration (cf. Németh et al., 2005).”
Background
Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease
Paula‐Lima, A. C., Brito‐Moreira, J., & Ferreira, S. T. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12304 · Cited by 170 · see citing works
Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory
Pocivavsek, A., Wu, H., Potter, M., Elmer, G., Pellicciari, R., & Schwarcz, R. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.127 · Cited by 171 · see citing works
“…the discovery of specific mechanisms controlling KYNA synthesis in the brain (Gramsbergen et al, 1997) and, in particular, by reports of abnormal KYNA levels in nervous tissue and body fluids in a host of neurological and psychiatric disorders (for review see Chen et al, 2009; Nemeth et al, 2005).”
Background
Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway
Török, N., Tanaka, M., & Vécsei, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249338 · Cited by 152 · see citing works
“of ROS which contributes to the depletion of endogenous antioxidants and the lipid peroxidation [12].”
BackgroundSelf-citation
The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation.
Maes, M. H. J., Mihaylova, I., Ruyter, M. D., Kubera, M., & Bosmans, E. (2007) · PubMed · Cited by 126 · see citing works
Interferon-gamma-inducible kynurenines/pteridines inflammation cascade: implications for aging and aging-associated psychiatric and medical disorders
Oxenkrug, G. (2010) · Journal of neural transmission · doi:10.1007/s00702-010-0475-7 · Cited by 121 · see citing works
“(Németh et al. 2005).”
The Janus-face kynurenic acid
Rózsa, É., Robotka, H., Vécsei, L., et al. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0052-5 · Cited by 125 · see citing works
“It has been shown, for instance, that KYNA can also noncompetitively block the activity of presynaptic a7-nACh receptors, and can increase the expression of non-a7-nACh receptors (Hilmas et al. 2001; Swartz et al. 1990; Nemeth et al. 2005).”
BackgroundSelf-citation
Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease
Bonda, D., Mailankot, M., Stone, J. G., Garrett, M. R., Staniszewska, M. M., Castellani, R. J., Siedlak, S. L., Zhu, X., Lee, H., Perry, G. L., et al. (2010) · Redox Report · doi:10.1179/174329210x12650506623645 · Cited by 125 · see citing works
Presence of kynurenic acid in food and honeybee products
Turski, M., Turska, M., Zgrajka, W., et al. (2008) · Amino Acids · doi:10.1007/s00726-008-0031-z · Cited by 115 · see citing works
“The conversion from tryptophan to kynurenine is achieved by tryptophan-2,3-dioxygenase and indole-2,3dioxygenase and KYNA is produced irreversibly from kynurenine by the activity of kynurenine aminotransferases (Nemeth et al. 2005).”
Background
Activation of the kynurenine pathway and increased production of the excitotoxin quinolinic acid following traumatic brain injury in humans
Yan, E., Frugier, T., Lim, C. K., Heng, B., Sundaram, G., Tan, M., Rosenfeld, J. V., Walker, D. W., Guillemin, G., & Morganti-Kossmann, M. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0328-2 · Cited by 96 · see citing works
“KYNA and QUIN are end products of two distinct branches of the KP and are released at different concentrations in both normal and disease conditions [37].”
Background
Kynurenine pathway metabolism in human blood–brain–barrier cells: implications for immune tolerance & neurotoxicity
Owe‐Young, R., Webster, N. L., Mukhtār, M., Pomerantz, R. J., Smythe, G. A., Walker, D. W., Armati, P. J., Crowe, S. M., & Brew, B. J. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05241.x · Cited by 112 · see citing works
“KA is also is a non-competitive inhibitor of a7 nicotinic acetylcholine pre-synaptic receptors (Nemeth et al. 2005).”
Background
Biological phenotypes underpin the physio‐somatic symptoms of somatization, depression, and chronic fatigue syndrome
Anderson, G., Berk, M., & Maes, M. H. J. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12182 · Cited by 109 · see citing works
Immune Privilege as an Intrinsic CNS Property: Astrocytes Protect the CNS against T-Cell-Mediated Neuroinflammation
Gimsa, U., Mitchison, N. A., & Brunner-Weinzierl, M. C. (2013) · Mediators of Inflammation · doi:10.1155/2013/320519 · Cited by 100 · see citing works
Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid
Tóth, F., Cseh, E., & Vécsei, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010403 · Cited by 92 · see citing works
“onism and free radical production [40], while neuroprotection can be exerted by kynurenic”
BackgroundInfluentialSelf-citation
Kynurenine metabolism in health and disease
Kolodziej, L. R., Paleolog, E. M., & Williams, R. O. (2010) · Amino Acids · doi:10.1007/s00726-010-0787-9 · Cited by 90 · see citing works
“KA is a neuro-protective molecule, which can reduce activation of N-methyl-D-aspartate receptors (NMDAR) ( Nemeth et al. 2005 ).”
Background
Somatization, but not depression, is characterized by disorders in the tryptophan catabolite (TRYCAT) pathway, indicating increased indoleamine 2,3-dioxygenase and lowered kynurenine aminotransferase activity.
Maes, M. H. J., Gałecki, P., Verkerk, R. M., & Rief, W. (2011) · PubMed · Cited by 89 · see citing works
Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils
Gigler, G., Szénási, G., Simó, A., Lévay, G. I., Hársing, L. G., Sas, K., Vécsei, L., & Toldi, J. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.02.029 · Cited by 89 · see citing works
“The extensive literature (see the most recent reviews: Klivenyi et al., 2004; Nemeth et al., 2005) suggests that a sufficient elevation of the brain kynurenic acid content leads to a definite neuroprotective effect.”
BackgroundSelf-citation
Diagnostic classifications in depression and somatization should include biomarkers, such as disorders in the tryptophan catabolite (TRYCAT) pathway
Maes, M. H. J., & Rief, W. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2011.09.029 · Cited by 88 · see citing works
“, 2003), while kynurenic acid is the only endogenous antagonist at NMDARs and acts as an inhibitor of glutamate release (Németh et al., 2005).”
Background
Different inhibitory effects of kynurenic acid and a novel kynurenic acid analogue on tumour necrosis factor-α (TNF-α) production by mononuclear cells, HMGB1 production by monocytes and HNP1-3 secretion by neutrophils
Tiszlavicz, Z., Németh, B., Fülöp, F., Vécsei, L., Tápai, K., Ocsovszky, I., & Mándi, Y. (2011) · Naunyn-Schmiedeberg's Archives of Pharmacology · doi:10.1007/s00210-011-0605-2 · Cited by 89 · see citing works
“Kynurenic acid (KynA), an endogenous product of the tryptophan metabolism and a broad spectrum antagonist of excitatory amino acid receptors, may serve as a protective agent in neurological disorders (Stone 2000; Klivenyi et al. 2004; Nemeth et al. 2005; Sas et al. 2007; Gigler et al. 2007; Vamos et al. 2009).”
BackgroundSelf-citation
Altered tryptophan absorption and metabolism could underlie long-term symptoms in survivors of coronavirus disease 2019 (COVID-19)
Eroğlu, İ., Eroğlu, B. Ç., & Guven, G. S. (2021) · Nutrition · doi:10.1016/j.nut.2021.111308 · Cited by 80 · see citing works
Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice
Larkin, P. B., Sathyasaikumar, K. V., Notarangelo, F. M., Funakoshi, H., Nakamura, T., Schwarcz, R. M., & Muchowski, P. J. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.07.002 · Cited by 79 · see citing works
Astrocytic activation in relation to inflammatory markers during clinical exacerbation of relapsing-remitting multiple sclerosis
Rejdak, K., Petzold, A., Kocki, T., et al. (2007) · Journal of Neural Transmission · doi:10.1007/s00702-007-0667-y · Cited by 78 · see citing works
“which is neuroprotective (Nemeth et al., 2005).”
The microbiota and the gut-brain axis: insights from the temporal and spatial mucosal alterations during colonisation of the germfree mouse intestine
Aidy, S. E., Kunze, W., Bienenstock, J., & Kleerebezem, M. (2012) · Beneficial Microbes · doi:10.3920/bm2012.0042 · Cited by 72 · see citing works
“However, kynurenic acid, which is a potent neuroprotective (Németh et al., 2005), was repressed in a temporal and region-specific manner (Figure 3).”
Background
Kynurenic Acid Acts as a Signaling Molecule Regulating Energy Expenditure and Is Closely Associated With Metabolic Diseases
Zhen, D., Liu, J., Zhang, X. D., & Song, Z. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.847611 · Cited by 70 · see citing works
“While KYNA does not easily cross the blood-brain barrier, KYNA synthesized by brain cannot be directly exported to the periphery and vice versa (50).”
Background
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
Kuwano, N., Kato, T. A., Setoyama, D., Sato-Kasai, M., Shimokawa, N., Hayakawa, K., Ohgidani, M., Sagata, N., Kubo, H., Kishimoto, J., et al. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.01.014 · Cited by 69 · see citing works
“While peripheral kynurenic acid mostly does not cross the blood-brain-barrier (Nemeth et al., 2005), peripheral kynurenic acid may be involved in the pathophysiology of MDD through its antioxidative activity on reactive oxygen species (Lugo-Huitron et al.”
The role and mechanism of tryptophan – kynurenine metabolic pathway in depression
Gong, X., Chang, R., Zou, J., Tan, S., & Huang, Z. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2022-0047 · Cited by 69 · see citing works
16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy
Reinthaler, E. M., Lal, D., Lebon, S., Hildebrand, M. S., Dahl, H. M., Regan, B. M., Feucht, M., Steinböck, H., Neophytou, B., Ronen, G. M., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu306 · Cited by 65 · see citing works
“Intracerebral injection of quinolinic acid causes seizures in mice (73) and elevation of quinolinate levels in the human brain is associated with neurodegenerative disorders (74,75).”
Background
Kynurenines, neurodegeneration and Alzheimer’s disease
Kincses, Z. T., Toldi, J., & Vécsei, L. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01123.x · Cited by 67 · see citing works
“Alterations in the KYN pathway has been identified in several neurological and more specifically neurodegenerative diseases [56, 57], such as Huntington chorea [58], Parkinson’s disease [59–62], multiple sclerosis [63, 64], focal dystonia [65] and migraine [66–69].”
BackgroundSelf-citation
The molecular interaction between the glutamatergic, noradrenergic, dopaminergic and serotoninergic systems informs a detailed genetic perspective on depressive phenotypes
Drago, A., Crisafulli, C., Sidoti, A., & Serretti, A. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.05.009 · Cited by 68 · see citing works
Inflammation-Induced Catabolism of Tryptophan and Tyrosine in Acute Ischemic Stroke
Ormstad, H., Verkerk, R. M., Aass, H. C. D., Amthor, K.-F., & Sandvik, L. (2013) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-0097-2 · Cited by 65 · see citing works
“It is well known that the activation of excitatory amino acid receptors can play a role in several neurodegenerative disorders, including stroke (Nemeth et al. 2005).”
Background
The molecular aspects of oxidative & nitrosative stress and the tryptophan catabolites pathway (TRYCATs) as potential causes of depression
Wigner, P., Czarny, P. L., Gałecki, P., Su, K., & Śliwiński, T. (2017) · Psychiatry Research · doi:10.1016/j.psychres.2017.09.045 · Cited by 64 · see citing works
Association of Increased Treg Cell Levels With Elevated Indoleamine 2,3‐Dioxygenase Activity and an Imbalanced Kynurenine Pathway in Interferon‐Positive Primary Sjögren's Syndrome
Maria, N. I., van Helden-Meeuwsen, C. G., Brkić, Z., Paulissen, S. M. J., Steenwijk, E. C., Dalm, V. A. S. H., van Daele, P. L. A., van Hagen, P. M., Kroese, F. G. M., van Roon, J. A. G., et al. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39629 · Cited by 63 · see citing works
“/total (%) Pilocarpine 22/58 (38) 23/66 (35) NS Hydroxychloroquine 21/58 (36) 37/66 (56) NS Fluconazol 6/58 (10) 9/66 (14) NS Corticosteroids 9/58 (16) 7/66 (11) NS”
Background
Association between single nucleotide polymorphisms of TPH1 and TPH2 genes, and depressive disorders
Wigner, P., Czarny, P. L., Synowiec, E., Bijak, M., Białek, K. I., Talarowska, M. E., Gałecki, P., Szemraj, J., & Śliwiński, T. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13459 · Cited by 60 · see citing works
Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications
Tanaka, M., Szabó, Á., & Vécsei, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312767 · Cited by 62 · see citing works
“The KYN pathway is crucial in Trp metabolism, generating metabolites that play key roles in both the central nervous and immune systems [121–124].”
Self-citation
Duplication 16p11.2 in a child with infantile seizure disorder
Bedoyan, J. K., Kumar, R. A., Sudi, J., Silverstein, F. S., Ackley, T., Iyer, R. K., Christian, S. L., & Martin, D. M. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33415 · Cited by 58 · see citing works
“Elevation of quinolinate levels in the human brain has been postulated to be involved in the pathogenesis of neurodegenerative and seizure disorders [Nemeth et al., 2005; Vamos et al., 2009].”
Immunomodulatory Effects of Genetic Alterations Affecting the Kynurenine Pathway
Boros, F. A., & Vécsei, L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02570 · Cited by 58 · see citing works
Self-citation
Kynurenine diminishes the ischemia-induced histological and electrophysiological deficits in the rat hippocampus
Sas, K., Robotka, H., Rózsa, É., Ágoston, M., Szénási, G., Gigler, G., Marosi, M., Kis, Z., Farkas, T., Vécsei, L., et al. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.07.013 · Cited by 56 · see citing works
Self-citation
The role of tryptophan metabolism in postpartum depression
Duan, K., Ma, J., Wang, S., Huang, Z., Zhou, Y., & Yu, H. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-017-0178-y · Cited by 56 · see citing works
“Role of KYN metabolites in postpartum depression As indicated above, kynurenine is a precursor for a number of neuroregulatory products, including 3HK, QUIN and KYNA (Németh et al. 2005; 99.”
Background
Kynurenine Metabolism and Alzheimer’s Disease: The Potential Targets and Approaches
Sharma, V., Singh, T. G., Prabhakar, N. K., & Mannan, A. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03546-8 · Cited by 52 · see citing works
Inflammation-Related Disorders in the Tryptophan Catabolite Pathway in Depression and Somatization
Anderson, G., Maes, M. H. J., & Berk, M. (2012) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-398314-5.00002-7 · Cited by 54 · see citing works
“…the expression of a4b2 nicotinic acetylcholine receptors (nAChR), and acts as an antagonist of a7-nAChR (Han, Cai, Tagle, & Li, 2010; Németh et al., 2005). a4b2-nAChRs are implicated in perception, cognition, and emotion (Picciotto et al., 1995), whereas a7-nAChRs modulate cortex…”
BackgroundInfluential
Involvement of kynurenines in Huntington’s disease and stroke-induced brain damage
Stone, T. W., Forrest, C. M., Stoy, N. S., & Darlington, L. G. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0676-8 · Cited by 53 · see citing works
Potential Role of Neuroactive Tryptophan Metabolites in Central Fatigue: Establishment of the Fatigue Circuit
Yamashita, M. (2020) · International Journal of Tryptophan Research · doi:10.1177/1178646920936279 · Cited by 48 · see citing works
Depressive symptoms as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1
Murakami, Y., Ishibashi, T., Tomita, E., Imamura, Y., Tashiro, T., Watcharanurak, K., Nishikawa, M., Takahashi, Y., Takakura, Y., Mitani, S., et al. (2016) · Scientific Reports · doi:10.1038/srep29920 · Cited by 52 · see citing works
Gas chromatography/tandem mass spectrometry detection of extracellular kynurenine and related metabolites in normal and lesioned rat brain
Notarangelo, F. M., Wu, H., Macherone, A., et al. (2011) · Analytical Biochemistry · doi:10.1016/j.ab.2011.12.032 · Cited by 51 · see citing works
Implication of NMDA Receptors in the Antidyskinetic Activity of Cabergoline, CI-1041, and Ro 61-8048 in MPTP Monkeys with Levodopa-induced Dyskinesias
Ouattara, B., Belkhir, S., Morissette, M., Dridi, M., Samadi, P., Grégoire, L., Meltzer, L. T., & Paolo, T. D. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-008-9137-8 · Cited by 51 · see citing works
“KYNA antagonizes glutamate receptors (Nemeth et al. 2005) and was reported to reduce dyskinesias (Gregoire et al.”
Background
Essential Role of Excessive Tryptophan and its Neurometabolites in Fatigue
Yamamoto, T., Azechi, H., & Mary Board (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s031716710001266x · Cited by 49 · see citing works
A novel kynurenic acid analogue: a comparison with kynurenic acid. An in vitro electrophysiological study
Marosi, M., Nagy, D., Farkas, T., et al. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0346-2 · Cited by 48 · see citing works
“The neuroprotective potential of an increased level of KYNA in the central nervous system (CNS) has been investigated in a variety of neurological disorders (Németh et al. 2005; Sas et al. 2007; Stone et al. 2007).”
BackgroundSelf-citation
Neuroprotection achieved in the ischaemic rat cortex with l-kynurenine sulphate
Robotka, H., Sas, K., Ágoston, M., Rózsa, É., Szénási, G., Gigler, G., Vécsei, L., & Toldi, J. (2008) · Life Sciences · doi:10.1016/j.lfs.2008.02.014 · Cited by 45 · see citing works
“The extensive literature (see the recent reviews by Klivenyi et al., 2004; Nemeth et al., 2005) suggests that an appropriate elevation of the brain KYNA concentration leads to a neuroprotective effect.”
BackgroundSelf-citation
The Peripheral Antinociceptive Effects of Endomorphin-1 and Kynurenic Acid in the Rat Inflamed Joint Model
Mecs, L., Tuboly, G., Nagy, E., Benedek, G., & Horváth, G. (2009) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3181b21c5e · Cited by 44 · see citing works
“It is produced endogenously both centrally and peripherally.(25) Our earlier data have revealed that intrathecally administered KYNA produced antinociception, but the effective dose caused motor impairment as well.”
BackgroundResult
Increased Plasma Kynurenic Acid Levels are Associated with Impaired Attention/Vigilance and Social Cognition in Patients with Schizophrenia
Huang, X., Ding, W., Wu, F., Zhou, S., Deng, S., & Ning, Y. (2020) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s239763 · Cited by 43 · see citing works
Dysfunction of neurotransmitter metabolism is associated with the severity of depression in first-diagnosed, drug-naïve depressed patients
Zhao, T., Liu, T., Wang, L., et al. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.01.023 · Cited by 39 · see citing works
Metabolic Biosynthesis of Potato (Solanum tuberosuml.) Antioxidants and Implications for Human Health
Lovat, C., Nassar, A. M. K., Kubow, S. J., Li, X., & Donnelly, D. J. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.830208 · Cited by 38 · see citing works
“Kynurenic acid is subsequently generated from kynurenine by kynurenine aminotransferase (Nemeth et al., 2005; Turski et al., 2011).”
Background
Metabolomic and proteomic characterization of sng and pain phenotypes in fibromyalgia
Hsu, W., Han, D., Ku, W., Chao, Y., Chen, C., & Lin, Y. (2021) · European Journal of Pain · doi:10.1002/ejp.1871 · Cited by 38 · see citing works
“reported an increased level of kynurenine, an intermediate in the major pathway for tryptophan degradation (Hackshaw et al., 2013; Nemeth et al., 2005), and decreased levels of serotonin (5- hydroxytryptamine, 5HT) and tryptophan, in serum of FM patients (Heils et al.”
Background
Synthesis and biological effects of some kynurenic acid analogs
Nagy, K., Plangár, I., Tuka, B., et al. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.10.029 · Cited by 37 · see citing works
Self-citation
Kynurenine Metabolites and Migraine: Experimental Studies and Therapeutic Perspectives
Fejes, A., Párdutz, Á., Toldi, J., & Vécsei, L. (2011) · Current Neuropharmacology · doi:10.2174/157015911795596621 · Cited by 37 · see citing works
“KYNA could potentially have therapeutic effects in neurological disorders [75, 111, 112] via the above-described receptor inhibitory effects, but its use as a neuroprotective agent is rather restricted because it has only a very limited ability to cross the blood–brain barrier [69].”
BackgroundSelf-citation
Pneumococcal meningitis causes accumulation of neurotoxic kynurenine metabolites in brain regions prone to injury
Bellac, C. L., Coimbra, R. S., Christen, S., & Leib, S. L. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.07.014 · Cited by 38 · see citing works
“The kynurenine (KYN) pathway is induced in other diseases associated with inflammation leading to brain injury, such as multiple sclerosis, AIDS-dementia complex and cerebral malaria (Nemeth et al., 2005; Stone, 2001, 2003).”
Background
Determination of kynurenic acid in human serum and its correlation with the concentration of certain amino acids
Fukushima, T., Mitsuhashi, S., Tomiya, M., et al. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2006.09.019 · Cited by 37 · see citing works
Alteration of kynurenic acid concentration in rat plasma following optically pure kynurenine administration: A comparative study between enantiomers
Fukushima, T., Sone, Y., Mitsuhashi, S., et al. (2008) · Chirality · doi:10.1002/chir.20620 · Cited by 36 · see citing works
The inimitable kynurenic acid: The roles of different ionotropic receptors in the action of kynurenic acid at a spinal level
Tuboly, G., Tar, L., Bohár, Z., et al. (2015) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.02.001 · Cited by 33 · see citing works
Self-citation
Saliva metabolomic profile of COVID-19 patients associates with disease severity
Sharif‐Askari, N. S., Soares, N. C., Mohamed, H. A., Sharif‐Askari, F. S., Alsayed, H. A. H., Al-Hroub, H. M., Salameh, L. I. J., Osman, R., Mahboub, B. H., Hamid, Q. A., et al. (2022) · Metabolomics · doi:10.1007/s11306-022-01936-1 · Cited by 32 · see citing works
The l ‐kynurenine–probenecid combination reduces neuropathic pain in rats
Pineda-Farías, J. B., Pérez‐Severiano, F., González‐Esquivel, D. F., et al. (2013) · European Journal of Pain · doi:10.1002/j.1532-2149.2013.00305.x · Cited by 32 · see citing works
“Once produced, kynurenic acid is actively extruded from the central nervous system by organic anion transporters (Németh et al., 2005; Uwai et al., 2012).”
Background
Human kynurenine aminotransferase II – reactivity with substrates and inhibitors
Passera, E., Campanini, B., Rossi, F., et al. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08106.x · Cited by 31 · see citing works
β-adrenergic enhancement of brain kynurenic acid production mediated via cAMP-related protein kinase A signaling
Luchowska, E., Kloc, R., Olajossy, B., et al. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.02.002 · Cited by 30 · see citing works
“KYNA blocks the glycine co-agonist site of N-methyl-D-aspartate (NMDA) receptor (Németh et al., 2005) and affects α-amino-3-hydroxy-5methyl-4-isoxazole propionic acid (AMPA) receptors — either facil-”
A bloodspot-based diagnostic test for fibromyalgia syndrome and related disorders
Hackshaw, K. V., RODRIGUEZ‐SAONA, L. E., Plans, M., Bell, L. N., & Buffington, C. A. T. (2013) · The Analyst · doi:10.1039/c3an36615d · Cited by 30 · see citing works
Chronic sleep restriction in the rotenone Parkinson’s disease model in rats reveals peripheral early-phase biomarkers
Fagotti, J., Targa, A., Rodrigues, L. S., Noseda, A. C. D., Dorieux, F. W. C., Scarante, F. F., Ilkiw, J. L., Louzada, F. M., Chowdhury, N. R., van der Veen, D. R., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-37657-6 · Cited by 29 · see citing works
Disturbance of neurotransmitter metabolism in drug-naïve, first-episode major depressive disorder: a comparative study on adult and adolescent cohorts
Wang, L., Yang, P., Yang, C., Yang, D. H., Wu, X., Cao, T., Zeng, C., Chen, Q., Zhang, S., Zhu, Z., et al. (2022) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-022-01406-8 · Cited by 33 · see citing works
“KYN could be catabolized into two active metabolites: the neuroprotective KYNA and neurotoxicity QA [11].”
BackgroundInfluential
Somatic Drugs for Psychiatric Diseases: Aspirin or Simvastatin for Depression?
Rahola, J. G. (2012) · Current Neuropharmacology · doi:10.2174/157015912800604533 · Cited by 27 · see citing works
“Quinolinic acid causes a dose-dependent decrease in cholinergic circuits and may empty dopamine, choline, GABA and encephalin deposits [129-133].”
Background
Determination of kynurenine levels in rat plasma by high-performance liquid chromatography with pre-column fluorescence derivatization
Mitsuhashi, S., Fukushima, T., Tomiya, M., et al. (2006) · Analytica Chimica Acta · doi:10.1016/j.aca.2006.11.040 · Cited by 28 · see citing works
Chromatographic Fingerprint Analysis, Acetylcholinesterase Inhibitory Properties and Antioxidant Activities of Redflower Ragleaf (C rassocephalum Crepidioides) Extract
Adefegha, S. A., Oboh, G., Molehin, O. R., Saliu, J. A., Athayde, M. L., & Boligon, A. A. (2015) · Journal of Food Biochemistry · doi:10.1111/jfbc.12200 · Cited by 26 · see citing works
Modifications on the carboxylic function of kynurenic acid
Fülöp, F., Szatmári, I., Toldi, J., et al. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0721-7 · Cited by 26 · see citing works
“, together with probenecid (200 mg/kg), which is effective in blocking NMDA receptors (Nemeth et al. 2005), 2 was similarly or even more effective in reducing the amplitude of the population spikes (Nagy et al.”
BackgroundSelf-citation
Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis
de Souza, F. R. S., Fontes-Dantas, F. L., da Silva, T. A., et al. (2011) · BMC Medical Genetics · doi:10.1186/1471-2350-12-51 · Cited by 26 · see citing works
“The KYN pathway is also induced in other diseases associated with inflammation-induced brain injury, such as Huntington’s disease [21], schizophrenia [22], multiple sclerosis AIDS-dementia complex and cerebral malaria [23,24].”
Changes in Extracellular Kynurenic Acid Concentrations in Rat Prefrontal Cortex After d-Kynurenine Infusion: An In vivo Microdialysis Study
Ogaya, T., Song, Z., Ishii, K., et al. (2009) · Neurochemical Research · doi:10.1007/s11064-009-0099-1 · Cited by 25 · see citing works
A More Holistic Perspective of Alzheimer's Disease: Roles of Gut Microbiome, Adipocytes, HPA Axis, Melatonergic Pathway and Astrocyte Mitochondria in the Emergence of Autoimmunity
Anderson, G. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2812355 · Cited by 24 · see citing works
“Given that 60% of brain kynurenine is derived from the periphery [112], systemic processes that drive large kynurenine increases, such as from white adipocyte (WAT) in obesity [113], can drive significant changes in the CNS relevant to dementia pathophysiology, including depriving tryptophan for…”
Background
Kynurenines and Neurofilament Light Chain in Multiple Sclerosis
Pukoli, D., Polyák, H., Rajda, C., & Vécsei, L. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.658202 · Cited by 22 · see citing works
“…IDO, indoleamine 2,3-dioxygenase; KAT, kynurenine aminotransferase; KMO, kynurenine 3-monooxygenase; MAO, monoamine oxidase; NAD+, nicotinamide adenine dinucleotide; QPRT, quinolinate phosphoribosyltransferase; TDO, tryptophan 2,3-dioxygenase. stress (Németh et al., 2005).”
Self-citation
Kynurenine pathway and its role in neurologic, psychiatric, and inflammatory bowel diseases
Sheibani, M., Shayan, M., Khalilzadeh, M., Soltani, Z. E., Jafari‐Sabet, M., Ghasemi, M., & Dehpour, A. R. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08859-7 · Cited by 24 · see citing works
Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension
Baalbaki, N., Blankestijn, J. M., Abdel‐Aziz, M. I., Backer, J. D., Bazdar, S., Beekers, I., Beijers, R. J. H. C. G., van den Bergh, J. P., Bloemsma, L. D., Bogaard, H. J., et al. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13071060 · Cited by 21 · see citing works
“Metabolites of kynurenine may cause neurotoxicity which can lead to fatigue complaints in long COVID patients [21].”
Background
The potential role of kynurenines in Alzheimer’s disease: pathomechanism and therapeutic possibilities by influencing the glutamate receptors
Majláth, Z., Toldi, J., & Vécsei, L. (2013) · Journal of Neural Transmission · doi:10.1007/s00702-013-1135-5 · Cited by 21 · see citing works
“The metabolites produced in this metabolic cascade, collectively termed kynurenines, are involved in a number of physiological processes, including neurotransmission and immune responses (Nemeth et al. 2005; Vecsei et al. 2013).”
BackgroundSelf-citation
Synthesis of New C-3 Substituted Kynurenic Acid Derivatives
Lőrinczi, B., Csámpai, A., Fülöp, F., et al. (2020) · Molecules · doi:10.3390/molecules25040937 · Cited by 21 · see citing works
“KYNA (kynurenic acid) is an endogenous product of the tryptophan (TRP) metabolism, a pathway known to be responsible for the production of nicotinamide adenine dinucleotide (NAD+) and NAD phosphate (NADP+) [1,2].”
Background
The IDO genetic polymorphisms and postpartum depressive symptoms: an association study in Chinese parturients who underwent cesarean section
Duan, K., Wang, S., Yin, J., Li, X., Ma, J., Huang, Z., Zhou, Y., Yu, H., Yang, M., Zhou, H., et al. (2018) · Archives of Women s Mental Health · doi:10.1007/s00737-018-0898-y · Cited by 21 · see citing works
Kynurenic acid selectively reduces heart rate in spontaneously hypertensive rats
Bądzyńska, B., Zakrocka, I. N., Turski, W. A., et al. (2019) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-019-01771-7 · Cited by 19 · see citing works
“Kynurenic acid (KYNA), a tryptophan metabolite, is formed from L-kynurenine (KYN) by kynurenine aminotransferases (KATs) (Németh et al. 2005).”
Background
Time-course of kynurenic acid concentration in mouse serum following the administration of a novel kynurenic acid analog
Zádori, D., Ilisz, I., Klivènyi, P., et al. (2011) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2011.02.014 · Cited by 19 · see citing works
Self-citation
The pentylenetetrazole-induced activity in the hippocampus can be inhibited by the conversion of l-kynurenine to kynurenic acid: An in vitro study
Rózsa, É., Robotka, H., Nagy, D., et al. (2008) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2007.12.001 · Cited by 19 · see citing works
Self-citation
The L-kynurenine signalling pathway in trigeminal pain processing: A potential therapeutic target in migraine?
Guo, S., Vécsei, L., & Ashina, M. (2011) · Cephalalgia · doi:10.1177/0333102411404717 · Cited by 20 · see citing works
“A growing body of evidence indicates that KYNA has a mediatory and modulatory role for glutamate and its receptors in peripheral and central pain processing (25,37,47,48).”
BackgroundSelf-citation
Determination of rat brain kynurenic acid by column‐switching HPLC with fluorescence detection
Fukushima, T., Mitsuhashi, S., Tomiya, M., et al. (2007) · Biomedical Chromatography · doi:10.1002/bmc.786 · Cited by 19 · see citing works
The Omics Landscape of Long COVID —A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery
Baalbaki, N., Slob, E. M. A., Kazer, S. W., Abdel‐Aziz, M. I., Bogaard, H. J., Golebski, K., & der Zee, A. H. M. (2025) · Allergy · doi:10.1111/all.16526 · Cited by 18 · see citing works
“The expression of IDO2 is moreover linked to decreased levels of tryptophan and increased kynurenine quantities, which have been proposed to cause fatigue symptoms [48].”
The Usefulness of the Low-FODMAP Diet with Limited Tryptophan Intake in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome
Chojnacki, C. J., Popławski, T., Błońska, A., Konrad, P., Chojnacki, J., & Błasiak, J. (2023) · Nutrients · doi:10.3390/nu15081837 · Cited by 17 · see citing works
The Interactions Between Kynurenine, Folate, Methionine and Pteridine Pathways in Obesity.
Engin, A., & Engin, A. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-48382-5_22 · Cited by 13 · see citing works
Prolonged therapy with antidepressants increases hippocampal level of kynurenic acid and expression of Kat1 and Kat2 genes
Kocki, T., Urbańska, E. M., Kocki, J., Kloc, R., Kocka, K., Olajossy, M., & Owe‐Larsson, B. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.01.004 · Cited by 17 · see citing works
Experimental diabetes mellitus type 1 increases hippocampal content of kynurenic acid in rats
Chmiel-Perzyńska, I., Perzyński, A., & Urbańska, E. M. (2014) · Pharmacological Reports · doi:10.1016/j.pharep.2014.07.014 · Cited by 17 · see citing works
Memantine increases brain production of kynurenic acid via protein kinase A-dependent mechanism
Kloc, R., Luchowska, E., Wielosz, M., Owe‐Larsson, B., & Urbańska, E. M. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.02.027 · Cited by 17 · see citing works

Altered tryptophan metabolism in Parkinson's disease: A possible novel therapeutic approach
Szabó, N., Kincses, Z. T., Toldi, J., & Vécsei, L. (2011) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2011.07.021 · Cited by 68 · see citing works
Self-citation
IMMUNE SYSTEM RELATED METABOLIC AND GENETIC ASPECTS IN DEPRESSIVE DISORDERS
Myint, A.-M. (2010) · University of Zagreb University Computing Centre (SRCE)
Endogenous neurotoxins from tryptophan
Stone, T. W. (2001) · Toxicon · doi:10.1016/s0041-0101(00)00156-2 · Cited by 147 · see citing works
Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease
Knapskog, A., Aksnes, M., Edwin, T. H., Ueland, P. M., Ulvik, A., Fang, E. F., Eldholm, R. S., Halaas, N. B., Saltvedt, I. T., Giil, L. M., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13162 · Cited by 50 · see citing works
L18 Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites
Breda, C., Sathyasaikumar, K. V., Sograte‐Idrissi, S., et al. (2016) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-314597.273 · Cited by 3 · see citing works

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)
DOI: 10.2174/1567202054368326
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Role of Kynurenines in the Central and Peripherial Nervous Systems

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cited by

Related

Record

About these checks