kynurenine

Summary

Top Publications

  1. ncbi Tryptophan and the immune response
    John R Moffett
    Department of Anatomy, Uniformed Services University of the Health Sciences, Building C, Room 2109, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
    Immunol Cell Biol 81:247-65. 2003
  2. pmc Kynurenine is an endothelium-derived relaxing factor produced during inflammation
    Yutang Wang
    Centre for Vascular Research, School of Medical Sciences Pathology and Bosch Institute, Faculty of Medicine, University of Sydney, Sydney, Australia
    Nat Med 16:279-85. 2010
  3. pmc Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase
    Guido Frumento
    Immunogenetics Laboratory, National Cancer Research Institute, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy
    J Exp Med 196:459-68. 2002
  4. pmc Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites
    Peter Terness
    Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, 69120 Heidelberg, Germany
    J Exp Med 196:447-57. 2002
  5. pmc Inflammation-associated depression: from serotonin to kynurenine
    Robert Dantzer
    Integrative Immunology and Behavior Program, Department of Animal Sciences, 227 Edward R Madigan Laboratory, 1201 West Gregory Drive, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Psychoneuroendocrinology 36:426-36. 2011
  6. ncbi Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease
    Luigina Romani
    Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
    Nature 451:211-5. 2008
  7. pmc Interleukin-1β: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis
    Patricia A Zunszain
    Section of Perinatal Psychiatry and Stress, Psychiatry and Immunology SPI Lab, Department of Psychological Medicine, Institute of Psychiatry, King s College London, London, UK
    Neuropsychopharmacology 37:939-49. 2012
  8. ncbi Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism
    Gregory F Oxenkrug
    Department of Psychiatry, Tufts University Tufts Medical Center, Boston, Massachusetts 02111, USA
    Ann N Y Acad Sci 1199:1-14. 2010
  9. ncbi Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO
    Maria L Belladonna
    Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06126, Italy
    J Immunol 177:130-7. 2006
  10. ncbi IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity
    M C Wichers
    Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
    Mol Psychiatry 10:538-44. 2005

Detail Information

Publications334 found, 100 shown here

  1. ncbi Tryptophan and the immune response
    John R Moffett
    Department of Anatomy, Uniformed Services University of the Health Sciences, Building C, Room 2109, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
    Immunol Cell Biol 81:247-65. 2003
    ..mediate tolerance are not well understood, but recent findings have implicated tryptophan catabolism through the kynurenine metabolic pathway as one of many mechanisms involved...
  2. pmc Kynurenine is an endothelium-derived relaxing factor produced during inflammation
    Yutang Wang
    Centre for Vascular Research, School of Medical Sciences Pathology and Bosch Institute, Faculty of Medicine, University of Sydney, Sydney, Australia
    Nat Med 16:279-85. 2010
    Control of blood vessel tone is central to vascular homeostasis. Here we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (Ido) expressed in endothelial cells contributes to arterial vessel relaxation and ..
  3. pmc Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase
    Guido Frumento
    Immunogenetics Laboratory, National Cancer Research Institute, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy
    J Exp Med 196:459-68. 2002
    ..The inhibitory role of tryptophan and of its catabolites was then tested. In the presence of tryptophan, only L-kynurenine and picolinic acid inhibit cell proliferation. In a tryptophan-free medium cell proliferation was not affected...
  4. pmc Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites
    Peter Terness
    Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, 69120 Heidelberg, Germany
    J Exp Med 196:447-57. 2002
    ..Transgenic DCs decreased the concentration of tryptophan, increased the concentration of kynurenine, the main tryptophan metabolite, and suppressed allogeneic T cell proliferation in vitro...
  5. pmc Inflammation-associated depression: from serotonin to kynurenine
    Robert Dantzer
    Integrative Immunology and Behavior Program, Department of Animal Sciences, 227 Edward R Madigan Laboratory, 1201 West Gregory Drive, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Psychoneuroendocrinology 36:426-36. 2011
    ..activation of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase that generates potentially neurotoxic kynurenine metabolites such as 3-hydroxy kynurenine and quinolinic acid...
  6. ncbi Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease
    Luigina Romani
    Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
    Nature 451:211-5. 2008
    ..Here we show that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained Vgamma1(+) ..
  7. pmc Interleukin-1β: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis
    Patricia A Zunszain
    Section of Perinatal Psychiatry and Stress, Psychiatry and Immunology SPI Lab, Department of Psychological Medicine, Institute of Psychiatry, King s College London, London, UK
    Neuropsychopharmacology 37:939-49. 2012
    ..Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1β induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), ..
  8. ncbi Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism
    Gregory F Oxenkrug
    Department of Psychiatry, Tufts University Tufts Medical Center, Boston, Massachusetts 02111, USA
    Ann N Y Acad Sci 1199:1-14. 2010
    ..is transcriptional induction of indoleamine 2,3-dioxygenase (IDO), rate-limiting enzyme of tryptophan (TRY)-kynurenine (KYN) pathway, by pro-inflammatory cytokines (PIC)...
  9. ncbi Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO
    Maria L Belladonna
    Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06126, Italy
    J Immunol 177:130-7. 2006
    ..initiated by IDO, that are still unclear, including the role of enzymes that are downstream of IDO in the kynurenine pathway and the role of the associated production of kynurenines...
  10. ncbi IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity
    M C Wichers
    Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
    Mol Psychiatry 10:538-44. 2005
    ..The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-alpha-..
  11. ncbi The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells
    Francesca Fallarino
    Department of Experimental Medicine, University of Perugia, Perugia, Italy
    J Immunol 176:6752-61. 2006
    ....
  12. ncbi T cell apoptosis by tryptophan catabolism
    F Fallarino
    Department of Experimental Medicine, University of Perugia, Italy
    Cell Death Differ 9:1069-77. 2002
    ..We show here that tryptophan metabolites in the kynurenine pathway, such as 3-hydroxyanthranilic and quinolinic acids, will induce the selective apoptosis in vitro of ..
  13. pmc An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells
    Joshua D Mezrich
    Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 7375, USA
    J Immunol 185:3190-8. 2010
    ..In this paper, we demonstrate that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the AHR...
  14. pmc Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism
    Nam Trung Nguyen
    Laboratory of Immune Regulation, Osaka University World Premier International Immunology Frontier Research Center, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 107:19961-6. 2010
    ..indoleamine 2,3-dioxygenase (IDO) expression, an immunosuppressive enzyme that catabolizes tryptophan into kynurenine (Kyn) and other metabolites in DC...
  15. pmc Tryptophan kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder: the serotonin hypothesis revisited 40 years later
    Gregory F Oxenkrug
    Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts 02111, USA
    Isr J Psychiatry Relat Sci 47:56-63. 2010
    ..corticosteroids levels, and metabolism of tryptophan is shunted away from serotonin production, and towards kynurenine production...
  16. ncbi IDO expression in the brain: a double-edged sword
    Erik Kwidzinski
    Institute of Cell Biology and Neurobiology, Charite, Berlin, Germany
    J Mol Med (Berl) 85:1351-9. 2007
    ..enzyme indoleamine-2,3-dioxygenase (IDO) initiates the first and rate-limiting step of the kynurenine pathway...
  17. ncbi Monitoring tryptophan metabolism in chronic immune activation
    Katharina Schröcksnadel
    Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz Pregl Strasse 3 A 6020 Innsbruck, Austria
    Clin Chim Acta 364:82-90. 2006
    ..generation of neurotransmitter 5-hydroxytryptamine (serotonin) by tryptophan 5-hydroxylase, and the formation of kynurenine derivatives and nicotinamide adenine dinucleotides...
  18. ncbi Effect of systemic kynurenine on cortical spreading depression and its modulation by sex hormones in rat
    Virginie Chauvel
    Cephalic Pain Unit of GIGA Neurosciences, Liege University, CHU Sart Tilman, T4, 1, 4000 Liege, Belgium
    Exp Neurol 236:207-14. 2012
    ..Kynurenic acid, a derivative of tryptophan metabolism, is an endogenous NMDA receptor antagonist whose cerebral concentrations can be augmented by systemic administration of its precursor L-kynurenine.
  19. ncbi The kynurenine system and immunoregulation
    Yvette Mandi
    Department of Medical Microbiology and Immunobiology, University of Szeged, Dom ter 10, 6720, Szeged, Hungary
    J Neural Transm 119:197-209. 2012
    ..A considerable amount of evidence has accumulated as concerns interactions between the kynurenine pathway, cytokines and the nervous system...
  20. ncbi Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities
    Robert Schwarcz
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA
    J Pharmacol Exp Ther 303:1-10. 2002
    Degradation of the essential amino acid tryptophan along the kynurenine pathway (KP) yields several neuroactive intermediates, including the free radical generator 3-hydroxykynurenine, the excitotoxic N-methyl-D-aspartate (NMDA) receptor ..
  21. pmc Tryptophan/kynurenine metabolism in human leukocytes is independent of superoxide and is fully maintained in chronic granulomatous disease
    Suk See De Ravin
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 116:1755-60. 2010
    ..Based on recent mouse studies, the lack of O(2)(·)-dependent interferon γ (IFNγ)-induced synthesis of kynurenine (kyn), an anti-inflammatory tryptophan metabolite produced by indolamine 2,3 deoxygenase (IDO), was proposed as ..
  22. ncbi More rapid method for simultaneous measurement of tryptophan and kynurenine by HPLC
    Andreas Laich
    Institute for Medical Chemistry and Biochemistry, Leopold Franzens University, A 6020 Innsbruck, Austria
    Clin Chem 48:579-81. 2002
  23. pmc Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer
    A Huang
    Department of Surgery, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK
    Br J Cancer 86:1691-6. 2002
    ..Serum tryptophan, kynurenine, neopterin, interleukin 2 soluble receptor alpha (IL-2 sRalpha), soluble tumour necrosis factor receptor I (sTNF ..
  24. ncbi Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders
    Katalin Sas
    Department of Neurology, University of Szeged, POB 427, H 6701 Szeged, Hungary
    J Neurol Sci 257:221-39. 2007
    ..Other pathogenetic factors are also briefly surveyed. The second part of the review deals with the kynurenine metabolic pathway, its alterations and their potential association with cellular energy impairment in certain ..
  25. ncbi Increased cortical kynurenate content in schizophrenia
    R Schwarcz
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    Biol Psychiatry 50:521-30. 2001
    BACKGROUND: Metabolites of the kynurenine pathway of tryptophan degradation may play a role in the pathogenesis of several human brain diseases...
  26. pmc L-Kynurenine, an amino acid identified as a sex pheromone in the urine of ovulated female masu salmon
    Hidenobu Yambe
    Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
    Proc Natl Acad Sci U S A 103:15370-4. 2006
    ..Bioassay-guided fractionation yielded an active compound that was identical to L-kynurenine in spectral and chromatographic properties. L-Kynurenine is a major metabolite of L-tryptophan in vertebrates...
  27. pmc Reversal of the Kynurenine pathway of tryptophan catabolism may improve depression in ART-treated HIV-infected Ugandans
    Priscilla Martinez
    Norwegian Center for Addiction Research, University of Oslo, Oslo, Norway Alcohol Research Group, School of Public Health, University of California, Berkeley, CA Center for Global Health, Massachusetts General Hospital, Boston, MA Division of Global Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, MA Mbarara University of Science and Technology, Mbarara, Uganda University of California at San Francisco, San Francisco, CA Division of HIV AIDS, San Francisco General Hospital, University of California San Francisco, CA Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA Department of Global Health and Population, Harvard School of Public Health, Boston, MA and Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Boston, MA
    J Acquir Immune Defic Syndr 65:456-62. 2014
    ..We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3-dioxygenase-1 and potentially other sources) may correlate ..
  28. ncbi Systemic markers of interferon-γ-mediated immune activation and long-term prognosis in patients with stable coronary artery disease
    Eva Ringdal Pedersen
    Section for Cardiology, Institute of Medicine, University of Bergen, 5021 Bergen, Norway
    Arterioscler Thromb Vasc Biol 31:698-704. 2011
    ..In activated macrophages, IFN-γ stimulates production of neopterin and conversion of tryptophan to kynurenine. We evaluated the relationships of plasma neopterin and plasma kynurenine:tryptophan ratio (KTR) to long-term ..
  29. ncbi Tryptophan catabolism via kynurenine production in Streptomyces coelicolor: identification of three genes coding for the enzymes of tryptophan to anthranilate pathway
    F P Zummo
    Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Universita degli Studi di Palermo, Viale delle Scienze Edificio 16, 90128 Palermo, Italy
    Appl Microbiol Biotechnol 94:719-28. 2012
    Most enzymes involved in tryptophan catabolism via kynurenine formation are highly conserved in Prokaryotes and Eukaryotes...
  30. ncbi Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection
    Trevor W Stone
    Institute for Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
    FEBS J 279:1386-97. 2012
    The oxidative pathway for the metabolism of tryptophan along the kynurenine pathway generates quinolinic acid, an agonist at N-methyl-D-aspartate receptors, as well as kynurenic acid which is an antagonist at glutamate and nicotinic ..
  31. ncbi Excessive tryptophan catabolism along the kynurenine pathway precedes ongoing sepsis in critically ill patients
    J P Zeden
    Department of Immunology, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
    Anaesth Intensive Care 38:307-16. 2010
    It has recently been shown that an increased plasma level of the tryptophan catabolite kynurenine is an early indicator for the development of sepsis in major trauma patients...
  32. ncbi NAD biosynthesis evolution in bacteria: lateral gene transfer of kynurenine pathway in Xanthomonadales and Flavobacteriales
    Wanessa C Lima
    Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
    Mol Biol Evol 26:399-406. 2009
    ..by two distinct pathways, namely, the bacterial aspartate (aspartate-to-quinolinate) and the eukaryotic kynurenine (tryptophan-to-quinolinate)...
  33. ncbi Increasing production of homocysteine and neopterin and degradation of tryptophan with older age
    Barbara Frick
    Institute of Medical Chemistry and Biochemistry, Leopold Franzens University, Innsbruck, Austria
    Clin Biochem 37:684-7. 2004
    ..Homocysteine is known to be elevated in the elderly, which is possibly due to an insufficient availability of folate, B6, and/or B12...
  34. pmc CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression
    C L Raison
    Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Psychiatry 15:393-403. 2010
    Cytokine-induced activation of indoleamine 2,3-dioxygenase (IDO) catabolizes L-tryptophan (TRP) into L-kynurenine (KYN), which is metabolized to quinolinic acid (QUIN) and kynurenic acid (KA)...
  35. ncbi Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders
    Sophie Erhardt
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    CNS Drugs 23:91-101. 2009
    The kynurenine pathway constitutes the main route of tryptophan degradation and generates the production of several neuroactive compounds; quinolinic acid is an excitotoxic NMDA receptor agonist, 3-hydroxykynurenine is a free-radical ..
  36. pmc Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice
    J C O'Connor
    Integrative Immunology and Behavior, Department of Animal Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana Champaign, Urbana, IL, USA
    Mol Psychiatry 14:511-22. 2009
    ..Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in ..
  37. pmc N-formylkynurenine as a marker of high light stress in photosynthesis
    Tina M Dreaden
    School of Chemistry and Biochemistry and Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA
    J Biol Chem 286:22632-41. 2011
    ..Reactive oxygen species reactions lead to oxidative damage of the reaction center, D1 protein turnover, and inhibition of electron transfer. Our results are consistent with a role for the CP43 NFK modification in photoinhibition...
  38. pmc Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder
    M Elizabeth Sublette
    Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, United States
    Brain Behav Immun 25:1272-8. 2011
    ..inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP)...
  39. ncbi Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer
    Yuzo Suzuki
    Department of Internal Medicine, Hamamatsu University School of Medicine, 1 20 1 Hanadayama Higashiku, Hamamatsu, Shizuoka 431 3125, Japan
    Lung Cancer 67:361-5. 2010
    Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation along the kynurenine (Kyn) pathway. By depleting tryptophan, IDO is considered to be a fundamental immune escape mechanism for tumor cells...
  40. ncbi IFN-beta1b induces kynurenine pathway metabolism in human macrophages: potential implications for multiple sclerosis treatment
    G J Guillemin
    Centre for Immunology, St Vincent s Hospital, Sydney, Australia
    J Interferon Cytokine Res 21:1097-101. 2001
    ..The kynurenine pathway (KP) is chiefly activated by IFN-gamma and IFN-alpha, leading to the production of a variety of ..
  41. ncbi Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway
    S R Thomas
    The Biochemistry Group, The Heart Research Institute, Sydney, New South Wales, Australia
    Redox Rep 4:199-220. 1999
    ..moiety of L-tryptophan (Trp) and other indoleamines and represents the initial and rate-limiting enzyme of the kynurenine (Kyn) pathway...
  42. pmc The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington's disease
    Susanna Campesan
    Department of Genetics, University of Leicester, Leicester LE1 7RH, UK
    Curr Biol 21:961-6. 2011
    Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation have been implicated in the pathophysiology of neurodegenerative disorders, including Huntington's disease (HD) [1]...
  43. ncbi Indoleamine 2,3-dioxygenase and regulatory function: tryptophan starvation and beyond
    Ciriana Orabona
    Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    Methods Mol Biol 677:269-80. 2011
    ..As a result, IDO(+) DCs mediate multiple effects on T lymphocytes, including inhibition of proliferation, apoptosis, and differentiation toward a regulatory phenotype...
  44. ncbi Tryptophan pyrrolase of rabbit intestine. D- and L-tryptophan-cleaving enzyme or enzymes
    S Yamamoto
    J Biol Chem 242:5260-6. 1967
  45. ncbi Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients
    M P Heyes
    Section on Analytical Biochemistry, NIMH, NIH, Bethesda, MD 20892
    J Neuroimmunol 40:71-80. 1992
    ..acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway...
  46. ncbi The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function
    Mariella Della Chiesa
    DIMS Dipartimento di Medicina Sperimentale, Universita di Genova, Genova, Italy
    Blood 108:4118-25. 2006
    ..In this study, we also demonstrate that natural killer (NK)-cell function can be influenced by IDO. Indeed, l-kynurenine, a Trp-derived catabolite resulting from IDO activity, was found to prevent the cytokine-mediated up-regulation ..
  47. ncbi Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms
    Jörg C Schefold
    Department of Nephrology and Intensive Care, Charite University Medicine, Campus Virchow Clinic, Berlin, Germany
    Nephrol Dial Transplant 24:1901-8. 2009
    ..Here we investigate Trp catabolism, IDO activity and the role of inflammation in moderate to very severe CKD and haemodialysis...
  48. pmc HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells
    Adriano Boasso
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20815, USA
    Blood 109:3351-9. 2007
    ..enzyme that inhibits T-cell proliferation by catabolizing the essential amino acid tryptophan (Trp) into the kynurenine (kyn) pathway...
  49. ncbi Tryptophan as a link between psychopathology and somatic states
    Sascha Russo
    Department of Biological Psychiatry, University Hospital Groningen, The Netherlands
    Psychosom Med 65:665-71. 2003
    ..Several somatic illnesses are associated with psychiatric comorbidity. Evidence is provided that availability of the essential amino acid tryptophan, which is the precursor of serotonin, may cause this phenomenon...
  50. pmc The activity of the immunoregulatory enzyme indoleamine 2,3-dioxygenase is decreased in smokers
    M Pertovaara
    Department of Microbiology and Immunology, University of Tampere, Medical School, Tampere, Finland
    Clin Exp Immunol 145:469-73. 2006
    ..IDO), an enzyme involved in the degradation of the essential amino acid tryptophan (trp) to its main metabolite kynurenine (kyn), suppresses T cell activity...
  51. ncbi The kynurenine pathway of tryptophan degradation as a drug target
    Robert Schwarcz
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    Curr Opin Pharmacol 4:12-7. 2004
    In mammalian cells, the essential amino acid tryptophan is degraded primarily by the kynurenine pathway, a cascade of enzymatic steps containing several biologically active compounds...
  52. ncbi Concurrent quantification of quinolinic, picolinic, and nicotinic acids using electron-capture negative-ion gas chromatography-mass spectrometry
    G A Smythe
    Ray Williams Biomedical Mass Spectrometry Facility, UNSW, Wallace Wurth Building, Faculty of Medicine, Sydney, New South Wales, 2052, Australia
    Anal Biochem 301:21-6. 2002
    Quinolinic, picolinic, and nicotinic acids and nicotinamide are end products of the kynurenine pathway from l-tryptophan and are intermediates in the biosynthesis of nicotinamide adenine dinucleotide...
  53. ncbi Expression of the kynurenine pathway enzymes in human microglia and macrophages
    Gilles J Guillemin
    Centre for Immunology, St Vincent s Hospital, Sydney, Australia
    Adv Exp Med Biol 527:105-12. 2003
    There is good evidence that the kynurenine pathway (KP) and one of its products, quinolinic acid (QUIN) play a role in the pathogenesis of neurological diseases. Monocytic cells are known to be the major producers of QUIN...
  54. pmc A community-based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study
    D Theofylaktopoulou
    Section for Pharmacology, University of Bergen, Norway
    Clin Exp Immunol 173:121-30. 2013
    Circulating neopterin and kynurenine/tryptophan ratio (KTR) increase during inflammation and serve as markers of cellular immune activation, but data are sparse on other determinants of these markers and metabolites of the kynurenine ..
  55. pmc KynR, a Lrp/AsnC-type transcriptional regulator, directly controls the kynurenine pathway in Pseudomonas aeruginosa
    Claire A Knoten
    Department of Microbiology and Immunology, The Brody School of Medicine at East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
    J Bacteriol 193:6567-75. 2011
    ..P. aeruginosa is part of a small group of bacteria that use the kynurenine pathway to catabolize tryptophan...
  56. ncbi Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys
    Laurent Gregoire
    Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavillon and Faculty of Pharmacy, Laval University, Quebec, PQ, Canada
    Behav Brain Res 186:161-7. 2008
    ..KYNA synthesis was stimulated by prolonged systemic administration of the kynurenine 3-hydroxylase inhibitor Ro 61-8048...
  57. ncbi Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase
    J Breton
    Department of Biology, Pharmacia and Upjohn, Nerviano, Italy
    Eur J Biochem 267:1092-9. 2000
    The mitochondrial outer membrane enzyme kynurenine 3-hydroxylase (K3H) is an NADPH-dependent flavin mono-oxygenase involved in the tryptophan pathway, where it catalyzes the hydroxylation of kynurenine...
  58. ncbi Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway
    Y Dang
    Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
    Free Radic Biol Med 28:615-24. 2000
    ..These enzymes catalyze the rate-limiting step in the kynurenine (KYN) pathway from trp to quinolinic acid (QA) with TDO in kidney and liver and IDO in many tissues, including ..
  59. ncbi Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type 4 metabotropic glutamate receptors
    F Fazio
    Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy
    Mol Pharmacol 81:643-56. 2012
    Cinnabarinic acid is an endogenous metabolite of the kynurenine pathway that meets the structural requirements to interact with glutamate receptors...
  60. ncbi Kynurenine concentration of serum was increased by exercise
    Y Ito
    Department of Physiology, School of Health Sciences, Fujita Health University, Aichi, Japan
    Adv Exp Med Biol 467:717-22. 1999
    b>Kynurenine pathway of tryptophan makes a lot of physiological active substances, such as quinolinate, NAD and so on, suggesting that kynurenine itself may play a very important role physiologically...
  61. ncbi Tryptophan depletion in depressed patients occurs independent of kynurenine pathway activation
    Martina M Hughes
    Neuroimmunology Research Group, Department of Physiology, School of Medicine and Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland
    Brain Behav Immun 26:979-87. 2012
    The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme indolamine 2,3-dioxygenase (IDO) have been implicated in the pathogenesis of depression...
  62. ncbi Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiency
    K Saito
    Department of Laboratory Medicine, Gifu University School of Medicine, Gifu 500 8705, Japan
    Am J Physiol Renal Physiol 279:F565-72. 2000
    Marked increases in metabolites of the L-tryptophan-kynurenine pathway, L-kynurenine and quinolinic acid (Quin), were observed in serum and cerebrospinal fluid (CSF) of both the rat and human with renal insufficiency...
  63. pmc Structural basis of kynurenine 3-monooxygenase inhibition
    Marta Amaral
    Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
    Nature 496:382-5. 2013
    Inhibition of kynurenine 3-monooxygenase (KMO), an enzyme in the eukaryotic tryptophan catabolic pathway (that is, kynurenine pathway), leads to amelioration of Huntington's-disease-relevant phenotypes in yeast, fruitfly and mouse models, ..
  64. ncbi Low plasma vitamin B-6 status affects metabolism through the kynurenine pathway in cardiovascular patients with systemic inflammation
    Oivind Midttun
    Bevital A S, Laboratoriebygget, 5021 Bergen, Norway
    J Nutr 141:611-7. 2011
    ..for suspected coronary heart disease, we investigated if plasma concentrations of any metabolites in the kynurenine pathway, which depend on PLP as cofactor, may serve as metabolic marker(s) of vitamin B-6 status...
  65. ncbi The kynurenine pathway in brain tumor pathogenesis
    Seray Adams
    Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
    Cancer Res 72:5649-57. 2012
    ..The kynurenine pathway (KP) is the principal route of L-tryptophan catabolism leading to the formation of the essential ..
  66. ncbi An expanding range of targets for kynurenine metabolites of tryptophan
    Trevor W Stone
    Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
    Trends Pharmacol Sci 34:136-43. 2013
    The kynurenine pathway of tryptophan metabolism accounts for most of the tryptophan that is not committed to protein synthesis and includes compounds active in the nervous and immune systems...
  67. ncbi Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications
    Gianpiera Ceresoli-Borroni
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    J Neurosci Res 85:845-54. 2007
    The kynurenine pathway (KP) of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid (KYNA) and, in a competing branch, the free radical generator 3-hydroxykynurenine (3-HK) and the ..
  68. ncbi Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats
    Nady Braidy
    University of New South Wales, Faculty of Medicine, Sydney, NSW, Australia
    FEBS J 278:4425-34. 2011
    The kynurenine pathway of tryptophan catabolism plays an important role in several biological systems affected by aging...
  69. ncbi Growth inhibition of multiresistant enterococci by interferon-gamma-activated human uro-epithelial cells
    C R MacKenzie
    Institute for Medical Microbiology and Virology, Heinrich Heine University, Dusseldorf, Germany
    J Med Microbiol 48:935-41. 1999
    ..analysis, at translational level by Western blot and also at a functional level by L-tryptophan degradation to L-kynurenine -- in the uro-epithelial cell line RT4...
  70. pmc The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*
    Jessica R Adams Wilson
    Vanderbilt University School of Medicine, Nashville, TN, USA
    Crit Care Med 40:835-41. 2012
    ..has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) ..
  71. ncbi Kynurenine pathway and disease: an overview
    Verónica Pérez-De La Cruz
    Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, S S A, Mexico
    CNS Neurol Disord Drug Targets 6:398-410. 2007
    b>Kynurenine pathway is gaining more and more attention every day in biomedical research since this catabolic route for tryptophan decomposition is not only implicated in different neurological disorders, but also possesses neuroactive ..
  72. pmc Pre- and postnatal exposure to kynurenine causes cognitive deficits in adulthood
    Ana Pocivavsek
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
    Eur J Neurosci 35:1605-12. 2012
    ..To this end, we stimulated KYNA formation by adding the KYNA precursor kynurenine (100 mg/day) to the chow fed to rat dams from gestational day 15 to postnatal day 21 (PD 21)...
  73. ncbi Highlights at the gate of tryptophan catabolism: a review on the mechanisms of activation and regulation of indoleamine 2,3-dioxygenase (IDO), a novel target in cancer disease
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    Amino Acids 37:219-29. 2009
    Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and rate-limiting step of Kynurenine pathway along the major route of Tryptophan catabolism...
  74. ncbi Effects of kynurenine metabolites on mesangial cell proliferation and gene expression
    Hiromitsu Yoshimura
    Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co, Ltd, Saitama shi, Saitama, Japan
    Exp Mol Pathol 87:70-5. 2009
    In the present study, we examined the effects of kynurenine metabolites on cultured mesangial cells (MCs) and demonstrated for the first time that they affect MC proliferation and gene expression...
  75. ncbi The kynurenine pathway in major depression: haplotype analysis of three related functional candidate genes
    Stephan Claes
    University Psychiatric Center K U Leuven, Campus Gasthuisberg, Leuven, Belgium
    Psychiatry Res 188:355-60. 2011
    ..One of the relevant metabolic pathways in this regard is the kynurenine pathway...
  76. ncbi Singlet-oxygen-mediated amino acid and protein oxidation: formation of tryptophan peroxides and decomposition products
    Michelle Gracanin
    The Heart Research Institute, Camperdown, NSW 2050, Australia
    Free Radic Biol Med 47:92-102. 2009
    ..This approach may allow the quantification of protein modification in intact cells arising from singlet oxygen formation...
  77. ncbi Anti-infectious activity of tryptophan metabolites in the L-tryptophan-L-kynurenine pathway
    Koji Narui
    Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan
    Biol Pharm Bull 32:41-4. 2009
    ..05). When the antimicrobial activity of the tryptophan metabolites in the L-tryptophan-L-kynurenine pathway was examined, 3-hydroxy-DL-kynurenine and alpha-picolinic acid had strong antibacterial activity against ..
  78. pmc The possible role of the kynurenine pathway in adolescent depression with melancholic features
    Vilma Gabbay
    NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, NY 10016, USA
    J Child Psychol Psychiatry 51:935-43. 2010
    ..MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP)...
  79. pmc Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia
    Ikwunga Wonodi
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA
    Schizophr Bull 36:211-8. 2010
    The brain concentration of kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation and antagonist at both the glycine coagonist site of the N-methyl-D-aspartic acid receptor (NMDAR) and the alpha7 nicotinic ..
  80. pmc Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease
    David J Bonda
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Redox Rep 15:161-8. 2010
    Tryptophan metabolism, through the kynurenine pathway, produces neurotoxic intermediates that are implicated in the pathogenesis of Alzheimer's disease...
  81. ncbi High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients
    Reetta Huttunen
    Department of Internal Medicine, Tampere University Hospital, University of Tampere Medical School, University of Tampere, Tampere, Finland
    Shock 33:149-54. 2010
    ..The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood ..
  82. ncbi Indoleamine 2,3-dioxigenase (IDO) is critical for host resistance against Trypanosoma cruzi
    Carolina Paola Knubel
    Centro de Investigaciones en Bioquímica Clínica e Inmunología Consejo Nacional de Investigaciones Científicas y Tecnicas, Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, 5000, Argentina
    FASEB J 24:2689-701. 2010
    ..cruzi amastigotes were sensitive to L-kynurenine downstream metabolites 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid, while 3-HK also affected the ..
  83. ncbi Comparative profiling of the mammalian mitochondrial proteome: multiple aconitase-2 isoforms including N-formylkynurenine modifications as part of a protein biomarker signature for reactive oxidative species
    Christian Hunzinger
    ProteoSys AG, Carl Zeiss Strasse 51, 55129 Mainz, Germany
    J Proteome Res 5:625-33. 2006
    ..g., reactive oxygen species (ROS), which induce N-formyl-kynurenine from oxidized tryptophans in certain mitochondrial proteins which are localized in close spatial proximity to ..
  84. ncbi Evidence for a key role of the peripheral kynurenine pathway in the modulation of anxiety- and depression-like behaviours in mice: focus on individual differences
    Anthony Laugeray
    UMRS Inserm U930, CNRS ERL 3106, Département des sciences du comportement, Universite Francois Rabelais, Tours, France
    Pharmacol Biochem Behav 98:161-8. 2011
    ..to the Unpredictable Chronic Mild Stress procedure (UCMS) resulted in peripheral and cerebral alterations of the kynurenine pathway (KP)...
  85. ncbi Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids
    Kittipong Maneechotesuwan
    Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    J Allergy Clin Immunol 121:43-50. 2008
    ..IDO inhibits eosinophilic inflammation in a murine asthma model, but little is known about its role in asthmatic patients or the effects of corticosteroids on this key regulatory enzyme...
  86. pmc A small-molecule screen identifies L-kynurenine as a competitive inhibitor of TAA1/TAR activity in ethylene-directed auxin biosynthesis and root growth in Arabidopsis
    Wenrong He
    State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Peking Tsinghua Center for Life Sciences, Beijing 100871, China
    Plant Cell 23:3944-60. 2011
    ..Using a chemical biology approach, we identified a small molecule, l-kynurenine (Kyn), which effectively inhibited ethylene responses in Arabidopsis thaliana root tissues...
  87. ncbi Plasma kynurenine and related measures in tic disorder patients
    Pieter J Hoekstra
    Department of Psychiatry, University Medical Center Groningen, University of Groningen, P O Box 660, 9700 AR, Groningen, The Netherlands
    Eur Child Adolesc Psychiatry 16:71-7. 2007
    Increased plasma kynurenine has been reported in tic disorder patients, and this observation has been suggested to be indicative of immune dysregulation...
  88. pmc An observational cohort study of the kynurenine to tryptophan ratio in sepsis: association with impaired immune and microvascular function
    Christabelle J Darcy
    Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia
    PLoS ONE 6:e21185. 2011
    ..indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to ..
  89. ncbi Neuropharmacology of quinolinic and kynurenic acids
    T W Stone
    Department of Pharmacology, University of Glasgow, Scotland
    Pharmacol Rev 45:309-79. 1993
    In a little more than 10 years, the kynurenine metabolites of tryptophan have emerged from their former position as biochemical curiosities, to occupy a prominent position in research on the causes and treatment of several major CNS ..
  90. pmc The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex
    Hui Qiu Wu
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    J Mol Neurosci 40:204-10. 2010
    ..we show here that nanomolar concentrations of KYNA, infused directly or produced in situ from its bioprecursor kynurenine, significantly decrease extracellular glutamate levels in the prefrontal cortex...
  91. ncbi Kynurenine and its metabolites in Alzheimer's disease patients
    E Gulaj
    Department of Geriatrics, Medical University, Bialystok, Poland
    Adv Med Sci 55:204-11. 2010
    The kynurenine pathway (KP) is a major route of tryptophan metabolism. Several metabolites of this pathway are proposed to be involved in the pathogenesis of Alzheimer's disease...
  92. ncbi Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils
    Gabor Gigler
    Division of Preclinical Research, EGIS Pharmaceuticals Plc, Budapest, Hungary
    Eur J Pharmacol 564:116-22. 2007
    ..The neuroprotective effect of L-kynurenine sulfate, a precursor of kynurenic acid, was therefore studied because L-kynurenine readily crosses the blood-..
  93. ncbi Kynurenines in the CNS: from endogenous obscurity to therapeutic importance
    T W Stone
    Institute of Biomedical and Life Sciences, University West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK
    Prog Neurobiol 64:185-218. 2001
    In just under 20 years the kynurenine family of compounds has developed from a group of obscure metabolites of the essential amino acid tryptophan into a source of intensive research, with postulated roles for quinolinic acid in ..
  94. ncbi Development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection
    T W Stone
    Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow, UK
    Trends Pharmacol Sci 21:149-54. 2000
    Manipulation of the kynurenine pathway of tryptophan metabolism has yielded a plethora of agents that are now being developed as neuroprotectants and anticonvulsants...
  95. ncbi Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway
    Helen J Ball
    Discipline of Pathology and Bosch Institute, University of Sydney, Camperdown, NSW 2006, Australia
    Int J Biochem Cell Biol 41:467-71. 2009
    The kynurenine pathway of tryptophan metabolism converts the amino acid tryptophan into a number of biologically active metabolites...
  96. ncbi Indoleamine 2,3-dioxygenase in infection: the paradox of an evasive strategy that benefits the host
    Teresa Zelante
    Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    Microbes Infect 11:133-41. 2009
    ..This review deals with recent findings that could gain IDO a reputation of Jack-of-all-trades in mammalian host/microbe interactions...
  97. ncbi l-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus
    Eniko Vamos
    Department of Neurology, University of Szeged, Szeged, Hungary
    Neuropharmacology 57:425-9. 2009
    ..play a crucial role in trigeminal pain processing, the aim of our experiments was to compare the effects of L-kynurenine (L-KYN) combined with probenecid (PROB) or with 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one ..
  98. ncbi Indoleamine 2,3-dioxygenase activity in nonagenarians is markedly increased and predicts mortality
    M Pertovaara
    Department of Microbiology and Immunology, University of Tampere, Medical School, Finland
    Mech Ageing Dev 127:497-9. 2006
    Indoleamine 2,3-dioxygenase (IDO), an enzyme degrading tryptophan (trp) to kynurenine (kyn), suppresses T cell activity. Ageing of the immune system, immunosenescence, includes a decline in T cell function...
  99. ncbi Increased plasma kynurenine values and kynurenine-tryptophan ratios after major trauma are early indicators for the development of sepsis
    Tim T Lögters
    Department of Trauma and Hand Surgery, University Hospital Dusseldorf, Germany
    Shock 32:29-34. 2009
    b>Kynurenine, the major degradation product of tryptophan has been shown to directly damage tissues, but its possible contribution to posttraumatic morbidity is unknown...
  100. ncbi Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation
    Michael Maes
    Department of Psychiatry, University Hospital of Maastricht, Postbus 5800, 6202 AZ Maastricht, The Netherlands
    Life Sci 71:1837-48. 2002
    ..The aims of the present study were to examine the effects of pregnancy and delivery on plasma kynurenine, a major tryptophan catabolite synthesized after induction of indoleamine-2, 3 dioxygenase (IDO) by pro-..
  101. pmc The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation
    Wei Chen
    Division of Hematology Oncology, Blood and Marrow Transplantation, Department of Pediatrics and The Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    J Immunol 181:5396-404. 2008
    ..Adding kynurenine, the immediate downstream metabolite of tryptophan, bypasses the 1-methyl-D-tryptophan effect and restores PDC-..

Research Grants63

  1. Tryptophan Metabolism, Genes, and Major Depression
    David Steffens; Fiscal Year: 2007
    ..The metabolism of tryptophan initiates in the liver and leads to formation of kynurenine. The concentrations of these compounds and constituents of other metabolic pathways can be analyzed through ..
  2. Neuroimaging abnormalities in major depressive disorder: effect of inflammation
    Jonathan Savitz; Fiscal Year: 2013
    ..of tryptophan (TRP), the precursor of serotonin, reducing serotonin levels and increasing the synthesis of kynurenine (KYN) and neurotoxic KYN metabolites, such as 3-hydroxykynurenine (3HK), and quinolinic acid (QUIN)...
  3. Phenotyping Major Depression with Increased Inflammation
    Andrew H Miller; Fiscal Year: 2013
    ..plasma and cerebrospinal fluid (CSF) concentrations of metabolites of indoleamine 2,3 dioxygenase including kynurenine, quinolinic acid and kynurenic acid, which has been shown to reduce dopamine release in the basal ganglia...
  4. Kynurenic Acid Synthesis in Mouse Brain
    Jianyong Li; Fiscal Year: 2010
    ..KYNA is produced by the kynurenine aminotransferase (KAT)-catalyzed transamination of kynurenine...
  5. Biomarkers of Aggressive Oral Cancer
    THEKKELNAYCKE RAJENDIRAN; Fiscal Year: 2013
    ..These metabolites included kynurenine, serine, glutathione, and glutamate/glutamic acid...
  6. Biobehavioral Role of Brain Kynurenine Metabolism in Mental Illness
    JASON C O'CONNOR; Fiscal Year: 2013
    ..enzyme indoleamine 2, 3 dioxygenase (IDO), which is the first and rate-limiting enzyme of the kynurenine pathway...
  7. MR SPECTROSCOPY TO REVEAL CNS MECHANISMS OF CYTOKINE-INDUCED BEHAVIORAL CHANGE
    Ebrahim Haroon; Fiscal Year: 2013
    ..will be associated with activation of CNS inflammatory responses and cytokine-induced increases in excitotoxic kynurenine metabolites, including quinolinic acid...
  8. EPR and Mossbauer Characterization of Mn and Fe Proteins, Models, Intermediates
    Michael P Hendrich; Fiscal Year: 2013
    ..The kynurenine pathway constitutes the major route of de novo biosynthesis of NAD, one of the essential redox cofactors in all ..
  9. Bupropion for Depression in ESRD Patients on Hemodialysis
    Pedro L Delgado; Fiscal Year: 2013
    ..cytokines, diminished total tryptophan (TRP), and increased levels of free TRP and the TRP catabolites kynurenine (KYN) and quinolinic acid...
  10. IDO Regulation in the SIV Model of HIV CNS Disease
    M Christine Zink; Fiscal Year: 2013
    ..This enzyme dampens cell-mediated immune responses by diverting tryptophan to kynurenine (Kyn) metabolism. Activation of the normally silent Kyn pathway results in draining of tryptophan reserves...
  11. Genetic Regulation of Indoleamine-2,3-dioxygenase and Psychiatric Complications o
    Gregory F Oxenkrug; Fiscal Year: 2010
    ..Literature suggests that the up-regulation of indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme of the kynurenine pathway of tryptophan (TRY) metabolism, is responsible for the depression, anxiety, and psychosis observed ..
  12. Identifying Epileptogenic Tubers in TSC
    Harry Chugani; Fiscal Year: 2013
    ..increased AMT uptake in the epileptogenic regions of TSC reflects increased metabolism of tryptophan along the kynurenine pathway (rather than the serotonin pathway) to produce endogenous convulsants, e.g., quinolinic acid...
  13. Proteinopathies of the Aging Central Nervous System
    Lennart Mucke; Fiscal Year: 2012
    ..Project 2, "Microglial Kynurenine Pathway and Selective Neuronal Vulnerability," will test if genetic or pharmacological inhibition of the ..
  14. Predictors and Targets of Response to Cytokine Antagonism in Depression
    Andrew H Miller; Fiscal Year: 2013
    ..symptom domains, neurocognitive testing, polysomnography, and serial blood samples that can be assayed for kynurenine (KYN) pathway activation and diurnal hypothalamic-pituitary-adrenal (HPA) axis activity...
  15. The Role of Microglia and the Kynurenine Pathway in Huntington's Disease
    Paul J Muchowski; Fiscal Year: 2012
    ..cerevisiae with single gene deletion strains that identified kynurenine 3-monooxygenase (KMO), an enzyme in the KP of tryptophan degradation, as a potent suppressor of mutant htt ..
  16. Mechanisms and novel therapy in intrauterine inflammation induced brain injury
    Sujatha Kannan; Fiscal Year: 2013
    ..Increased tryptophan metabolism by the kynurenine pathway induced by intrauterine inflammation may play a crucial role in the development of this injury...
  17. The Neuroimmunology of Anhedonia
    Vilma Gabbay; Fiscal Year: 2013
    ..We have studied the kynurenine pathway (KP), a central neuroimmunological pathway, which is activated by cytokines and degrades tryptophan into ..
  18. MAILLARD REACTIONS AND OXIDATION IN CATARACTOGENESIS
    Ram H Nagaraj; Fiscal Year: 2012
    ..Our preliminary data suggest that the dicarbonyl and kynurenine protein modification processes are related and interdependent...
  19. Indoleamine 2, 3 dioxygenase signaling and function in Type 1 Diabetes
    Suparna Sarkar; Fiscal Year: 2009
    ..IDO catalyzes the initial, rate-limiting step of Tryptophan (Trp) catabolism along the Kynurenine (Kyn) pathway...
  20. Tryptophan Metabolism in Human Brain Tumors
    Csaba Juhasz; Fiscal Year: 2012
    ..mainly via the immuno-modulatory enzyme indoleamine 2,3-dioxygenase (IDO), the rate-limiting step of the kynurenine pathway...
  21. Nicotinic receptors: Role in hippocampal synaptic function
    Edson X Albuquerque; Fiscal Year: 2012
    ..a7* nAChR activity is accompanied by increased brain levels of kynurenic acid (KYNA), an astrocyte-derived kynurenine metabolite that blocks a7* nAChRs and N-methyl-D-aspartate (NMDA) receptors J Neurosci 21:7463, 2001...
  22. Neopterin and kynurenine as predictors of depression risk and antiviral efficacy
    Gregory F Oxenkrug; Fiscal Year: 2013
    ..up-regulates rate-limiting enzymes of formation of neopterin, a by-product of pteridines biosynthesis, and kynurenine (KYN), a tryptophan (TRY) metabolite...
  23. Modulating AhR in tumor and lymphoid microenvironments via local drug delivery
    GREGORY SZETO; Fiscal Year: 2013
    ..2,3,7,8-tetrachlorodibenzo-p-dioxin) and endogenous compounds (such as the tryptophan-derived catabolic product kynurenine (Kyn) and photoproduct 6-formylindolo[3,2-b]carbazole)...
  24. Catalytic and Inhibitory Mechanisms in Indoleamine 2,3-dioxygenase
    Syun Ru Yeh; Fiscal Year: 2013
    ..provided by applicant): Indoleamine 2,3-dioxygenase (IDO) catalyzes the oxidation of L-tryptophan to N-formyl kynurenine. In contrast to the wide spectrum of P450 monooxygenases, IDO is one of the only two heme-based dioxygenases in ..
  25. Molecular Mechanisms of Protein Crosslinking in the Lens
    Ram H Nagaraj; Fiscal Year: 2013
    ..Kynurenines are tryptophan oxidation products produced by the kynurenine pathway initiated by indoleamine 2,3-dioxygenase. They are present in relatively high levels in human lenses...
  26. Pathogenesis of Fungal Keratitis
    Eric Pearlman; Fiscal Year: 2013
    ..in the cornea leading to recruitment of PMN-17 cells, and Aim 3 will examine IL-17 induced NADPH oxidase and kynurenine mediated ROS production by PMN-17 cells...
  27. The Kynurenine Pathway in Pulmonary Arterial Hypertension
    Debby Ngo; Fiscal Year: 2013
    ..This proposal builds on preliminary studies that have identified a novel association of metabolites in the kynurenine pathway with PAH...
  28. The interaction of IDO and Tregs Leads to Immunosuppression in Glioma
    DEREK ALAN WAINWRIGHT; Fiscal Year: 2013
    ..IDO is an inducible enzyme that converts the essential amino acid, tryptophan, to the metabolite, kynurenine (Kyn.)...
  29. Modulating anti-HIV immunity by plasmacytoid dendritic cells
    Nina Bhardwaj; Fiscal Year: 2013
    ..generation requires the expression of indolamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan to kynurenine, as it is reversed upon addition of the specific inhibitor 1 methyl-tryptophan...
  30. Modulating anti-HIV immunity by plasmacytoid dendritic cells
    Melissa Victoria Fernandez; Fiscal Year: 2013
    ..generation requires the expression of indolamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan to kynurenine, as it is reversed upon addition of the specific inhibitor 1 methyl-tryptophan...
  31. Organophosphorus Pesticide Toxicology
    JOHN CASIDA; Fiscal Year: 2006
    ..action by OP phosphorylation at a nucleophilic site coupled to the cannabinoid receptor-1 (CB1) agonist site; kynurenine formamidase (KFase) structure and function relative to teratogenesis and diazinon oxen action in the brain...
  32. Neuroprotective Effects of Estrogen in Serotonin Neurons
    Jessica Henderson; Fiscal Year: 2007
    ..of the proposed research is to determine the effects of estrogen administration after ovariectomy on the kynurenine pathway...
  33. TRYPTOPHAN METABOLISM IN MOSQUITOES
    Jianyong Li; Fiscal Year: 2007
    ..b>Kynurenine, 3-hydroxykynurenine (3-HK), kynurenic acid (KA) and xanthurenic acid (XA) are the key components in the ..
  34. CELLULAR FREE RADICAL TOXICITY MECHANISMS
    OLEN BROWN; Fiscal Year: 1999
    ..Quinolinic acid (QA), a metabolite of the brain kynurenine pathway from tryptophan, is the most potent endogenous excitatory and convulsive agent known, 100-X as potent as ..
  35. METHODS FOR KYNURENINE SYSTEM IN HUNTINGTON'S DISEASE
    Wayne Matson; Fiscal Year: 1990
    ..The long term goal of the work is to provide a data base and biochemical model of HD that can be used as a guide to develop therapeutic strategies...
  36. Imaging Serotonergic Transmission in HIV Depression
    Martin Pomper; Fiscal Year: 2006
    ..and from activated microglia within the central nervous system (CNS), may provoke hyperactivity of the kynurenine pathway, an alternative route of tryptophan metabolism that effectively depletes CNS 5-HT levels and produces ..
  37. Role of IDO in the age-related increase in severity of graft versus host disease
    Lisa K Jasperson; Fiscal Year: 2010
    ..novel methods of GVHD inhibition using the IDO pathway, both by inducing IDO pretransplant and by administering kynurenine metabolites, the downstream products of IDO activity...
  38. KYNURENINES, GLIA AND EPILEPSY
    Robert Schwarcz; Fiscal Year: 2006
    ..The regulatory mechanisms that normally control brain kynurenine pathway metabolism and function are impaired in chronic epilepsy...
  39. Genetic Polymorphism of a Schizophrenia Endophenotype
    Ikwunga Wonodi; Fiscal Year: 2007
    ..Deciphering the genetic mechanisms of prefrontal dopamine dysfunction in schizophrenia would advance our understanding of the pathophysiology of schizophrenia and may help identify novel treatments. [unreadable] [unreadable] [unreadable]..
  40. Imaging tryptophan metabolism in children with epilepsy
    Diane Chugani; Fiscal Year: 2007
    ..hypothesis of this proposal is that abnormalities in brain tryptophan metabolism via the serotonin and/or kynurenine pathways contribute to the pathophysiology and localization of neocortical epilepsy...
  41. IMAGING TRYPTOPHAN METABOLISM IN TUBEROUS SCLEROSIS
    Diane Chugani; Fiscal Year: 2003
    ..The central hypothesis of this proposal is that abnormalities tryptophan metabolism via the serotonergic and/or kynurenine pathways contribute to the pathophysiology of both epilepsy and autism in children with TSC...
  42. BRAIN SEROTONIN SYNTHESIS IN AUTISM
    Diane Chugani; Fiscal Year: 2001
    ..An understanding of the neurochemical disturbances in autism is important for the development of new treatment approaches. ..
  43. CNS DA NEURONS--CELLULAR BASIS OF PATTERNED ACTIVITY
    Paul Shepard; Fiscal Year: 2002
    ..abstract_text> ..
  44. PHOTOCHEMISTRY OF HUMAN RETINAL LIPOFUSCIN
    ELIZABETH GAILLARD; Fiscal Year: 2002
    ..Information from these studies may allow for the development of protocols to slow down or stop the processes that lead to irreversible damage to the human retina ..
  45. MEMBRANE DEFICITS AND OUTCOME IN SCHIZOPHRENIA
    Jeffrey Yao; Fiscal Year: 2003
    ..Also, the study will shed light on the significance of peripheral membrane dynamics to central membrane phospholipid metabolism over the early course of illness. ..
  46. Effects of Opioids on Sleep and Fatigue
    Joel Dimsdale; Fiscal Year: 2004
    ..abstract_text> ..
  47. Selective Induction of Estrogen Conjugative Metabolism
    Bao Ting Zhu; Fiscal Year: 2006
    ..These studies will also provide examinations of the important roles of bioactive estrogen metabolites (e.g., 4-OH-E2 and 16alpha-OH-E2) in estrogen-induced cancers. ..
  48. Modifications of Small Heat Shock Proteins in the Lens
    RAM NAGARAJ; Fiscal Year: 2009
    ..These studies will improve our understanding of the interplay between sHsps and metabolic pathways, and they will help us to define the role of sHsps in apoptosis of lens epithelial cells and the implications for cataract formation. ..
  49. Non-disulfide protein crosslinks in human lens
    Mikhail Linetsky; Fiscal Year: 2005
    ..The anticipated results should provide a solid basis for understanding the impact the formation of non-disulfide crosslinks has on the development of cataract in humans. ..
  50. Oxidative Stress Markers and HIV Dementia
    Ned Sacktor; Fiscal Year: 2009
    ..We believe that oxidative stress plays a significant role in the development of HIV-D, and strategies to decrease oxidative stress may serve as a useful therapeutic target to treat HIV-D. ..
  51. Novel Pathways of AGE Formation in Diabetes
    RAM NAGARAJ; Fiscal Year: 2005
    ..Our study is expected to provide novel insights into AGE formation in diabetes and may lead to new pharmacological agents to prevent AGE formation and complications in diabetes. ..
  52. Dietary Polyphenols Are Consequential Epigenetic Modulators of Gene Expression
    BAOTING ZHU; Fiscal Year: 2009
    ..It is expected that the outcomes of the proposed studies will have direct clinical utility in the near future and far-reaching human health implications. ..
  53. Neuroimmune Mechanisms of Glucocorticoid Resistance
    Andrew H Miller; Fiscal Year: 2010
    ..Taken together, these studies will help identify novel targets for the treatment of mood disorders in both medically ill and medically healthy patients. ..
  54. OXIDATIVE STRESS AND CATARACT FORMATION
    Shambhu D Varma; Fiscal Year: 2010
    ..Along with monitoring inhibition of lens opacification, mechanism of action of EP will be ascertained at the levels of morphology, histology, tissue metabolism and apoptotic changes. ..
  55. LEUKEMIA THERAPY WITH MIHA SPECIFIC T CELLS
    Wei Chen; Fiscal Year: 2002
    ..3. To develop methods develops for in vitro induction of MiHA-specific T cells for leukemia therapy. ..
  56. Arterial 5-HT Transporter Function
    Stephanie Watts; Fiscal Year: 2009
    ..abstract_text> ..
  57. Neuroimmunology of Behavioral and Mood Disorders
    Robert Dantzer; Fiscal Year: 2008
    ..These innovative experiments are needed to understand how functional interactions between the immune system and brain regulate behavior and mood . ..
  58. ADRENAL STEROID--IMMUNE INTERACTIONS
    Andrew Miller; Fiscal Year: 2003
    ..Further understanding of neuroendocrine- immune interactions in viral infections will provide the foundation for developing new therapeutic strategies to limit the immunologic and behavioral morbidity of viral diseases. ..
  59. Pathophysiology of IFN-alpha-induced Sleep Disturbances
    Andrew Miller; Fiscal Year: 2008
    ..Moreover, this work will identify novel targets for the development of treatment strategies for sleep alterations in medically ill patients. ..
  60. RNA directed silencing of HIV and SIV receptors
    Michael Murray; Fiscal Year: 2004
    ..abstract_text> ..
  61. 2-METHOXYESTRADIOL & HORMONAL CANCER
    Bao Ting Zhu; Fiscal Year: 2006
    ..The results will also provide novel mechanistic understanding for the biological actions of 2-MeO-E2. ..