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1

Maget, Alexander, Martina Platzer, Susanne A. Bengesser, Frederike T. Fellendorf, Armin Birner, Robert Queissner, Carlo Hamm, et al. "Differences in Kynurenine Metabolism During Depressive, Manic, and Euthymic Phases of Bipolar Affective Disorder." Current Topics in Medicinal Chemistry 20, no. 15 (June 1, 2020): 1344–52. http://dx.doi.org/10.2174/1568026619666190802145128.

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Background & Objectives: The kynurenine pathway is involved in inflammatory diseases. Alterations of this pathway were shown in psychiatric entities as well. The aim of this study was to determine whether specific changes in kynurenine metabolism are associated with current mood symptoms in bipolar disorder. Methods: Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms
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2

Badawy, Abdulla A. B., and Samina Bano. "Tryptophan Metabolism in Rat Liver after Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors." International Journal of Tryptophan Research 9 (January 2016): IJTR.S38190. http://dx.doi.org/10.4137/ijtr.s38190.

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Rat liver tryptophan (Trp), kynurenine pathway metabolites, and enzymes deduced from product/substrate ratios were assessed following acute and/or chronic administration of kynurenic acid (KA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), Trp, and the kynureninase inhibitors benserazide (BSZ) and carbidopa (CBD). KA activated Trp 2,3-dioxygenase (TDO), possibly by increasing liver 3-HAA, but inhibited kynurenine aminotransferase (KAT) and kynureninase activities with 3-HK as substrate. 3-HK inhibited kynureninase activity from 3-HK. 3-HAA stimulated TDO, but inhibited kynuren
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3

Ruddick, Jon P., Andrew K. Evans, David J. Nutt, Stafford L. Lightman, Graham A. W. Rook, and Christopher A. Lowry. "Tryptophan metabolism in the central nervous system: medical implications." Expert Reviews in Molecular Medicine 8, no. 20 (August 2006): 1–27. http://dx.doi.org/10.1017/s1462399406000068.

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The metabolism of the amino acid l-tryptophan is a highly regulated physiological process leading to the generation of several neuroactive compounds within the central nervous system. These include the aminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), products of the kynurenine pathway of tryptophan metabolism (including 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and kynurenic acid), the neurohormone melatonin, several neuroactive kynuramine metabolites of melatonin, and the trace amine tryptamine. The integral role of central serotonergic systems in the mo
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Majláth, Zsófia, and László Vécsei. "A kinureninrendszer és a stressz." Orvosi Hetilap 156, no. 35 (August 2015): 1402–5. http://dx.doi.org/10.1556/650.2015.30246.

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The kynurenine pathway is the main route of tryptophan degradation which gives rise to several neuroactive metabolites. Kynurenic acid is an endogenous antagonist of excitatory receptors, which proved to be neuroprotective in the preclinical settings. Kynurenines have been implicated in the neuroendocrine regulatory processes. Stress induces several alterations in the kynurenine metabolism and this process may contribute to the development of stress-related pathological processes. Irritable bowel disease and gastric ulcer are well-known disorders which are related to psychiatric comorbidity an
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5

Mieszkowski, Jan, Paulina Brzezińska, Błażej Stankiewicz, Andrzej Kochanowicz, Bartłomiej Niespodziński, Joanna Reczkowicz, Tomasz Waldziński, et al. "Direct Effects of Vitamin D Supplementation on Ultramarathon-Induced Changes in Kynurenine Metabolism." Nutrients 14, no. 21 (October 25, 2022): 4485. http://dx.doi.org/10.3390/nu14214485.

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In humans, most free tryptophan is degraded via kynurenine pathways into kynurenines. Kynurenines modulate the immune system, central nervous system, and skeletal muscle bioenergetics. Consequently, kynurenine pathway metabolites (KPMs) have been studied in the context of exercise. However, the effect of vitamin D supplementation on exercise-induced changes in KPMs has not been investigated. Here, we analyzed the effect of a single high-dose vitamin D supplementation on KPMs and tryptophan levels in runners after an ultramarathon. In the study, 35 amateur runners were assigned into two groups:
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Zakharov, Gennady A., Alexander V. Zhuravlev, Tatyana L. Payalina, Nikolay G. Kamyshev, and Elena V. Savvateeva-Popova. "The influence of D. melanogaster mutations of the kynurenine pathway of tryptophan metabolism on locomotor behavior and expression of genes belonging to glutamatergic and cholinergic systems." Ecological genetics 9, no. 2 (June 15, 2011): 65–73. http://dx.doi.org/10.17816/ecogen9265-73.

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Disbalance of kynurenines produced by Drosophila mutations of the kynurenine pathway of tryptophan metabolism influences the locomotor behavior in larvae. The most pronounced is the effect of accumulation of kynurenic acid in the mutant cinnabar manifested as sharp reduction of general level of locomotor activity. The mutations seem to act through modulatory influences of kynurenines on signal cascades governed by ionotropic glutamatergic and cholinergic receptors. Expression of receptor genes in the mutants shows age-related changes pointing to gradual evolvement of consequences of kynurenine
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7

Theofylaktopoulou, Despoina, Arve Ulvik, Øivind Midttun, Per Magne Ueland, Stein Emil Vollset, Ottar Nygård, Steinar Hustad, Grethe S. Tell та Simone J. P. M. Eussen. "Vitamins B2and B6as determinants of kynurenines and related markers of interferon-γ-mediated immune activation in the community-based Hordaland Health Study". British Journal of Nutrition 112, № 7 (8 серпня 2014): 1065–72. http://dx.doi.org/10.1017/s0007114514001858.

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Vitamins B2and B6are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of vitamins B2and B6as determinants of kynurenines and two markers of interferon-γ-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of vitamins B2and B6vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasm
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8

Martin, Kyle S., Michele Azzolini, and Jorge Lira Ruas. "The kynurenine connection: how exercise shifts muscle tryptophan metabolism and affects energy homeostasis, the immune system, and the brain." American Journal of Physiology-Cell Physiology 318, no. 5 (May 1, 2020): C818—C830. http://dx.doi.org/10.1152/ajpcell.00580.2019.

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Tryptophan catabolism through the kynurenine pathway generates a variety of bioactive metabolites. Physical exercise can modulate kynurenine pathway metabolism in skeletal muscle and thus change the concentrations of select compounds in peripheral tissues and in the central nervous system. Here we review recent advances in our understanding of how exercise alters tryptophan-kynurenine metabolism in muscle and its subsequent local and distal effects. We propose that the effects of kynurenine pathway metabolites on skeletal muscle, adipose tissue, immune system, and the brain suggest that some o
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9

Ashoura, Norah E., Joseph Dekker, Todd A. Triplett, Kendra Garrison, John Blazeck, Christos Karamitros, Candice Lamb, et al. "The Force Awakens: Illuminating the Role of Kynurenine in Cancer Progression and Treatment." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 240.16. http://dx.doi.org/10.4049/jimmunol.204.supp.240.16.

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Abstract Cancer is the second leading cause of death in the United States, with an estimated 40% of all Americans expected to be diagnosed with cancer in their lifetime. Despite progress in treatment options, major obstacles in current therapies must be overcome to limit their harmful side effects on patients. To evade immune clearance, many cancers elevate tryptophan (Trp) catabolism in the tumor microenvironment (TME) by upregulating the enzyme indoleamine 2,3-dioxygenase (IDO). As a result, cancer cells (1) monopolize extracellular tryptophan and (2) release L-kynurenine into the TME, an in
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10

Schlittler, Maja, Michel Goiny, Leandro Z. Agudelo, Tomas Venckunas, Marius Brazaitis, Albertas Skurvydas, Sigitas Kamandulis, et al. "Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans." American Journal of Physiology-Cell Physiology 310, no. 10 (May 15, 2016): C836—C840. http://dx.doi.org/10.1152/ajpcell.00053.2016.

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Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exerci
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Ervik, Arne Olav, Stein-Erik Hafstad Solvang, Jan Erik Nordrehaug, Per Magne Ueland, Øivind Midttun, Audun Hildre, Adrian McCann, Ottar Nygård, Dag Aarsland та Lasse Melvaer Giil. "The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ε4 Allele Variant in Patients With Dementia". International Journal of Tryptophan Research 12 (січень 2019): 117864691988563. http://dx.doi.org/10.1177/1178646919885637.

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Background: The apolipoprotein E ε4 gene variant (APOEε4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain. Aim: To assess whether the presence of at least one APOEε4 allele modifies the association between kynurenines and the cognitive prognosis. Methods: A total of 152 patients with sera for metabolite measurements and APOE genotype were included from the Dementia Study of Western Norway. The part
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12

Baran, H., J. A. Hainfellner, and B. Kepplinger. "Kynurenic Acid Metabolism in Various Types of Brain Pathology in HIV-1 Infected Patients." International Journal of Tryptophan Research 5 (January 2012): IJTR.S10627. http://dx.doi.org/10.4137/ijtr.s10627.

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Kynurenic acid, an intermediate metabolite of L-kynurenine, is a competitive antagonist of inotropic excitatory amino acid (EAA) receptors as well as a non competitive antagonist of 7 alpha nicotine cholinergic receptors and its involvement in memory deficit and cognition impairment has been suggested. Alterations of kynurenic acid metabolism in the brain after HIV-1 (human immunodeficiency virus type-1) infection have been demonstrated. The present study evaluates the biosynthetic machinery of kynurenic acid e.g. the content of L-kynurenine and kynurenic acid, as well as the activity of enzym
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13

Kepplinger, Berthold, Halina Baran, Brenda Sedlnitzky-Semler, Nagy-Roland Badawi, and Helene Erhart. "Stochastic Resonance Activity Influences Serum Tryptophan Metabolism in Healthy Human Subjects." International Journal of Tryptophan Research 4 (January 2011): IJTR.S7986. http://dx.doi.org/10.4137/ijtr.s7986.

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Background Stochastic resonance therapy (SRT) is used for rehabilitation of patients with various neuropsychiatric diseases. An alteration in tryptophan metabolism along the kynurenine pathway has been identified in the central and peripheral nervous systems in patients with neuroinflammatory and neurodegenerative diseases and during the aging process. This study investigated the effect of SRT as an exercise activity on serum tryptophan metabolites in healthy subjects. Methods Serum L-tryptophan, L-kynurenine, kynurenic acid, and anthranilic acid levels were measured one minute before SRT and
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14

Goeden, Nick, Francesca M. Notarangelo, Ana Pocivavsek, Sarah Beggiato, Alexandre Bonnin, and Robert Schwarcz. "Prenatal Dynamics of Kynurenine Pathway Metabolism in Mice: Focus on Kynurenic Acid." Developmental Neuroscience 39, no. 6 (2017): 519–28. http://dx.doi.org/10.1159/000481168.

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The kynurenine pathway (KP), the major catabolic route of tryptophan in mammals, contains several neuroactive metabolites, including kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). KP metabolism, and especially the fate of KYNA, during pregnancy is poorly understood, yet it may play a significant role in the development of psychiatric disorders later in life. The present study was designed to investigate the prenatal features of KP metabolism in vivo, with special focus on KYNA. To this end, pregnant CD-1 mice were treated systemically with kynurenine (100 mg/kg), KYNA (10 mg/kg), or sal
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15

Aarsland, Tore Ivar Malmei, Johanne Telnes Instanes, Maj-Britt Rocio Posserud, Arve Ulvik, Ute Kessler, and Jan Haavik. "Changes in Tryptophan-Kynurenine Metabolism in Patients with Depression Undergoing ECT—A Systematic Review." Pharmaceuticals 15, no. 11 (November 19, 2022): 1439. http://dx.doi.org/10.3390/ph15111439.

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The kynurenine pathway of tryptophan (Trp) metabolism generates multiple biologically active metabolites (kynurenines) that have been implicated in neuropsychiatric disorders. It has been suggested that modulation of kynurenine metabolism could be involved in the therapeutic effect of electroconvulsive therapy (ECT). We performed a systematic review with aims of summarizing changes in Trp and/or kynurenines after ECT and assessing methodological issues. The inclusion criterium was measures of Trp and/or kynurenines before and after ECT. Animal studies and studies using Trp administration or Tr
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16

Colle, R., C. Verstuyft, D. David, P. Chanson, and E. Corruble. "Peripheral tryptophan and serotonin and kynurenine pathways in major depression: A case-control study." European Psychiatry 64, S1 (April 2021): S328. http://dx.doi.org/10.1192/j.eurpsy.2021.880.

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IntroductionThe tryptophan pathway along with its two branches of metabolism to serotonin and kynurenine seems to be affected in major depression. In depressed patients, peripheral levels of tryptophan, serotonin, kynurenine and their metabolite remain unclear.ObjectivesTherefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC).MethodsFasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (se
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Bhat, Abid, Ananda Staats Pires, Vanessa Tan, Saravana Babu Chidambaram, and Gilles J. Guillemin. "Effects of Sleep Deprivation on the Tryptophan Metabolism." International Journal of Tryptophan Research 13 (January 2020): 117864692097090. http://dx.doi.org/10.1177/1178646920970902.

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Sleep has a regulatory role in maintaining metabolic homeostasis and cellular functions. Inadequate sleep time and sleep disorders have become more prevalent in the modern lifestyle. Fragmentation of sleep pattern alters critical intracellular second messengers and neurotransmitters which have key functions in brain development and behavioral functions. Tryptophan metabolism has also been found to get altered in SD and it is linked to various neurodegenerative diseases. The kynurenine pathway is a major regulator of the immune response. Adequate sleep alleviates neuroinflammation and facilitat
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18

Simonato, Manuela, Stefano Dall’Acqua, Caterina Zilli, Stefania Sut, Romano Tenconi, Nicoletta Gallo, Paolo Sfriso, et al. "Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome." Biomedicines 9, no. 11 (November 19, 2021): 1724. http://dx.doi.org/10.3390/biomedicines9111724.

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Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS pati
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Huhn, M., M. Herrero San Juan, B. Melcher, C. Dreis, K. Schmidt, J. M. Pfeilschifter, M. Vieth, J. Stein, and H. H. Radeke. "P110 Identification of the tryptophan metabolite 3-hydroxyanthranilic acid as a novel tool for the differentiation of Crohn’s disease phenotypes." Journal of Crohn's and Colitis 14, Supplement_1 (January 2020): S190—S191. http://dx.doi.org/10.1093/ecco-jcc/jjz203.239.

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Abstract Background The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise question regarding the unclarified heterogeneity of disease pathomechanisms. While biomarkers for the differentiation of Crohn’s disease (CD) vs. ulcerative colitis (UC) have been suggested, specific markers for a subclassification of CD phenotypes are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterise potential biomarkers focusing on the downstream metabolites of kynurenine m
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Beier, Ulf H., Michelle D. Cully, Peter J. Siska, Katrin Singer, Jing Jiao, Tara TeSlaa, William J. Quinn, et al. "Fatty acid depletion is a reversible cause of kynurenine induced T cell apoptosis." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 137.1. http://dx.doi.org/10.4049/jimmunol.202.supp.137.1.

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Abstract Metabolic conditions in the tumor microenvironment (TME) are a barrier for anti-tumor immunotherapy. The TME metabolite kynurenine binds aryl hydrocarbon receptor which has been linked to immunosuppressive effects. We questioned if kynurenines could be utilized for therapeutic immunosuppression, and examined the effect of kynurenines on human and murine effector T cell (Teff) metabolism and function. We co-stimulated C57BL/6 Teff for three days and measured bioenergetic function with Seahorse. Injection of 1 mM L- or D-kynurenine reduced extracellular acidification by 4.2 ±0.2 and 7.1
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Jonsson, William O., Jonathan Ponette, Oscar Horwath, Tomas Rydenstam, Karin Söderlund, Björn Ekblom, Michele Azzolini, Jorge L. Ruas, and Eva Blomstrand. "Changes in plasma concentration of kynurenine following intake of branched-chain amino acids are not caused by alterations in muscle kynurenine metabolism." American Journal of Physiology-Cell Physiology 322, no. 1 (January 1, 2022): C49—C62. http://dx.doi.org/10.1152/ajpcell.00285.2021.

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Administration of branched-chain amino acids (BCAA) has been suggested to enhance mitochondrial biogenesis, including levels of PGC-1α, which may, in turn, alter kynurenine metabolism. Ten healthy subjects performed 60 min of dynamic one-leg exercise at ∼70% of Wmax on two occasions. They were in random order supplied either a mixture of BCAA or flavored water (placebo) during the experiment. Blood samples were collected during exercise and recovery, and muscle biopsies were taken from both legs before, after, and 90 and 180 min following exercise. Ingestion of BCAA doubled their concentration
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Dehhaghi, Mona, Hamed Kazemi Shariat Panahi, and Gilles J. Guillemin. "Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status." International Journal of Tryptophan Research 12 (January 2019): 117864691985299. http://dx.doi.org/10.1177/1178646919852996.

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The kynurenine pathway is important in cellular energy generation and limiting cellular ageing as it degrades about 90% of dietary tryptophan into the essential co-factor NAD+ (nicotinamide adenine dinucleotide). Prior to the production of NAD+, various intermediate compounds with neuroactivity (kynurenic acid, quinolinic acid) or antioxidant activity (3-hydroxykynurenine, picolinic acid) are synthesized. The kynurenine metabolites can participate in numerous neurodegenerative disorders (Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease) or other disea
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Ala, Moein, and Seyed Parsa Eftekhar. "The Footprint of Kynurenine Pathway in Cardiovascular Diseases." International Journal of Tryptophan Research 15 (January 2022): 117864692210966. http://dx.doi.org/10.1177/11786469221096643.

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Kynurenine pathway is the main route of tryptophan metabolism and produces several metabolites with various biologic properties. It has been uncovered that several cardiovascular diseases are associated with the overactivation of kynurenine pathway and kynurenine and its metabolites have diagnostic and prognostic value in cardiovascular diseases. Furthermore, it was found that several kynurenine metabolites can differently affect cardiovascular health. For instance, preclinical studies have shown that kynurenine, xanthurenic acid and cis-WOOH decrease blood pressure; kynurenine and 3-hydroxyan
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Castro-Portuguez, Raul, Jeremy Meyers, Sam Freitas, Hope Dang, Emily Turner, Destiny DeNicola, Luis Espejo, and George Sutphin. "Kynurenine Metabolism Lifespan Extension Mediated by Oxidative Stress Response and Hypoxic Response in C. elegans." Innovation in Aging 5, Supplement_1 (December 1, 2021): 679–80. http://dx.doi.org/10.1093/geroni/igab046.2557.

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Abstract Aging is characterized by a progressive decline in the normal physiological functions of an organism, ultimately leading to mortality. Metabolic changes throughout the aging process disrupt the balance and homeostasis of the cell. The kynurenine metabolic pathway is the sole de novo biosynthetic pathway for producing NAD+ from ingested tryptophan. Altered kynurenine pathway activity is associated with both aging and a variety of age-associated diseases, and kynurenine-based interventions can extend lifespan in Caenorhabditis elegans. Our laboratory recently demonstrated knockdown of t
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Sadok, Ilona, and Magdalena Staniszewska. "Electrochemical Determination of Kynurenine Pathway Metabolites—Challenges and Perspectives." Sensors 21, no. 21 (October 28, 2021): 7152. http://dx.doi.org/10.3390/s21217152.

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In recent years, tryptophan metabolism via the kynurenine pathway has become one of the most active research areas thanks to its involvement in a variety of physiological processes, especially in conditions associated with immune dysfunction, central nervous system disorders, autoimmunity, infection, diabetes, and cancer. The kynurenine pathway generates several metabolites with immunosuppressive functions or neuroprotective, antioxidant, or toxic properties. An increasing body of work on this topic uncovers a need for reliable analytical methods to help identify and quantify tryptophan metabo
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Shestopalov, A. V., O. P. Shatova, M. S. Karbyshev, A. M. Gaponov, N. E. Moskaleva, S. A. Appolonova, A. V. Tutelyan, V. V. Makarov, S. M. Yudin, and S. A. Roumiantsev. "“Kynurenine switch” and obesity." Bulletin of Siberian Medicine 20, no. 4 (January 3, 2022): 103–11. http://dx.doi.org/10.20538/1682-0363-2021-4-103-111.

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Aim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection, the concentrations of several serum metabolites, such as kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, quinolinic acid, 5-hydroxyindole-3-acetate, tryptamine, serotonin, indole-3-lactate, indole-3-acetate, indole-3- butyrate, indole-3-carboxaldehyde, indole-3-acrylate, and indole
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Ciapała, Katarzyna, and Ewelina Rojewska. "Kinurenines in Central Nervous System under neuropathic pain – clinical implications from basic research." BÓL 20, no. 3 (January 16, 2020): 32–39. http://dx.doi.org/10.5604/01.3001.0013.7396.

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Central nervous system disorders are often accompanied by changes in tryptophan metabolism. Kynurenine pathway is known to be the main route by which this essential amino acid is catabolized to a plenty of metabolites. Intermediates of this cascade are responsible for a wide spectrum of effects, including endogenous regulation of neuronal excitability and immune cells response. Excessive or disrupted activation of the pathway can lead to the accumulation of neurotoxic compounds, and in consequence, contributes to the development of various type of pathologies. These aspects shed new light on t
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Navrotskaya, V. V., and Yu Yu Sapota. "Analysis of the role of kynurenine metabolism in drosophila viability control at the high sugar diet influence." Faktori eksperimental'noi evolucii organizmiv 26 (September 1, 2020): 72–76. http://dx.doi.org/10.7124/feeo.v26.1244.

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Aim. To analyze viability and life span of drosophila at genetic and pharmacological inhibition of tryptophan-kynurenine metabolism, when cultivating on the standard nutritive medium and at a high sugar diet. Methods. Wild type stock and the stock with vermilion mutation have been used. Viability (number of individuals, mortality at the pupal stage) and median life span of imagoes have been determined. Results. High sugar diet has been found to negatively affect the viability of drosophila, leading to increased mortality at the pupal stage and decrease of males’ life span; wild-type stock is l
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Kanova, Marcela, and Pavel Kohout. "Tryptophan: A Unique Role in the Critically Ill." International Journal of Molecular Sciences 22, no. 21 (October 28, 2021): 11714. http://dx.doi.org/10.3390/ijms222111714.

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Tryptophan is an essential amino acid whose metabolites play key roles in diverse physiological processes. Due to low reserves in the body, especially under various catabolic conditions, tryptophan deficiency manifests itself rapidly, and both the serotonin and kynurenine pathways of metabolism are clinically significant in critically ill patients. In this review, we highlight these pathways as sources of serotonin and melatonin, which then regulate neurotransmission, influence circadian rhythm, cognitive functions, and the development of delirium. Kynurenines serve important signaling functio
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Rentschler, Katherine M., Annalisa M. Baratta, Audrey L. Ditty, Nathan T. J. Wagner, Courtney J. Wright, Snezana Milosavljevic, Jessica A. Mong, and Ana Pocivavsek. "Prenatal Kynurenine Elevation Elicits Sex-Dependent Changes in Sleep and Arousal During Adulthood: Implications for Psychotic Disorders." Schizophrenia Bulletin 47, no. 5 (April 5, 2021): 1320–30. http://dx.doi.org/10.1093/schbul/sbab029.

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Abstract Dysregulation of the kynurenine pathway (KP) of tryptophan catabolism has been implicated in psychotic disorders, including schizophrenia and bipolar disorder. Kynurenic acid (KYNA) is a KP metabolite synthesized by kynurenine aminotransferases (KATs) from its biological precursor kynurenine and acts as an endogenous antagonist of N-methyl-D-aspartate and α7-nicotinic acetylcholine receptors. Elevated KYNA levels found in postmortem brain tissue and cerebrospinal fluid of patients are hypothesized to play a key role in the etiology of cognitive symptoms observed in psychotic disorders
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31

Allison, David J., Joshua P. Nederveen, Tim Snijders, Kirsten E. Bell, Dinesh Kumbhare, Stuart M. Phillips, Gianni Parise, and Jennifer J. Heisz. "Exercise training impacts skeletal muscle gene expression related to the kynurenine pathway." American Journal of Physiology-Cell Physiology 316, no. 3 (March 1, 2019): C444—C448. http://dx.doi.org/10.1152/ajpcell.00448.2018.

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Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, wheth
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32

Fellendorf, F., M. Platzer, A. Birner, R. Queissner, S. Bengesser, M. Lenger, A. Maget, et al. "Tryptophan metabolism in bipolar disorder." European Psychiatry 65, S1 (June 2022): S110. http://dx.doi.org/10.1192/j.eurpsy.2022.310.

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Introduction Immune mediated inflammatory processes are involved in the aetiopathogenesis of bipolar disorder (BD) and weight associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found more active in BD but also associated with overweight/obesity. Objectives Aims of our study were to investigate 1.) the tryptophan metabolism in BD compared to mentally healthy controls, 2.) differences in weight classes, 3.) in a longitudinal setting, dependent on the incidence of BD episodes and euthymia
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33

Noakes, Rowland R. "Effects of Tranilast on the Urinary Excretion of Kynurenic and Quinolinic Acid under Conditions of L Tryptophan Loading." International Journal of Tryptophan Research 6 (January 2013): IJTR.S12797. http://dx.doi.org/10.4137/ijtr.s12797.

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The pathogenesis of morphea and other cutaneous sclerosing disorders remain poorly understood. Although they are considered to be autoimmune disorders, abnormal tryptophan metabolism may be involved. Current therapy is directed to supressing the autoimmune response. Demonstration of a therapeutic response to manipulation of the kynurenine pathway would both support a role for abnormal tryptophan metabolism and offer additional targets for therapy. Tranilast is a 3-hydroxyanthranilic acid derivative known to target the kynurenine pathway. The aim of this study was to see if tranilast lowered th
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34

Nicholas, Dequina A., Lorena M. Salto, Kristen Lavelle, Joy Wilson, W. Lawrence Beeson, Anthony Firek, William H. R. Langridge, Zaida Cordero-MacIntyre, and Marino De Leon. "En Balance: The Contribution of Physical Activity to the Efficacy of Spanish Diabetes Education of Hispanic Americans with Type 2 Diabetes." Journal of Diabetes Research 2020 (April 21, 2020): 1–8. http://dx.doi.org/10.1155/2020/4826704.

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Purpose. En Balance, a culturally sensitive diabetes education program, improves glycemic control in Hispanics with type 2 diabetes. The program emphasized diet, physical activity, and other factors important for glycemic control. However, the individual contributions of these education factors are unclear. The purpose of this study is to assess the contribution of physical activity to the success of En Balance in improving the health of Mexican Americans with type 2 diabetes. Methods. A retrospective study was conducted with plasma samples collected pre- and post-3-month study. Samples from 5
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35

Hestad, Knut, Jan Alexander, Helge Rootwelt, and Jan O. Aaseth. "The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases." Biomolecules 12, no. 7 (July 18, 2022): 998. http://dx.doi.org/10.3390/biom12070998.

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Emerging evidence suggests that neuroinflammation is involved in both depression and neurodegenerative diseases. The kynurenine pathway, generating metabolites which may play a role in pathogenesis, is one of several competing pathways of tryptophan metabolism. The present article is a narrative review of tryptophan metabolism, neuroinflammation, depression, and neurodegeneration. A disturbed tryptophan metabolism with increased activity of the kynurenine pathway and production of quinolinic acid may result in deficiencies in tryptophan and derived neurotransmitters. Quinolinic acid is an N-me
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36

Hartai, Z., P. Klivenyi, T. Janaky, B. Penke, L. Dux, and L. Vecsei. "Kynurenine metabolism in multiple sclerosis." Acta Neurologica Scandinavica 112, no. 2 (August 2005): 93–96. http://dx.doi.org/10.1111/j.1600-0404.2005.00442.x.

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37

Baran, H., K. Jellinger, and L. Deecke. "Kynurenine metabolism in Alzheimer's disease." Journal of Neural Transmission 106, no. 2 (March 17, 1999): 165–81. http://dx.doi.org/10.1007/s007020050149.

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38

Badawy, Abdulla A.-B., Sarah L. Lake, and Donald M. Dougherty. "Mechanisms of the Pellagragenic Effect of Leucine: Stimulation of Hepatic Tryptophan Oxidation by Administration of Branched-Chain Amino Acids to Healthy Human Volunteers and the Role of Plasma Free Tryptophan and Total Kynurenines." International Journal of Tryptophan Research 7 (January 2014): IJTR.S18231. http://dx.doi.org/10.4137/ijtr.s18231.

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The pellagragenic effect of leucine (Leu) has been proposed to involve modulation of L-tryptophan (Trp) metabolism along the hepatic kynurenine pathway. Here, we discuss some of the mechanisms suggested and report the effects in healthy volunteers of single doses of Leu (4.05–6.75 g) administered in a 16-amino acid mixture on concentrations of plasma Trp and its kynurenine metabolites. Flux of Trp through Trp 2,3-dioxygenase (TDO) is dose-dependently enhanced most probably by Leu and can be attributed to TDO activation. Trp oxidation is better expressed using plasma total kynurenines, rather t
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Chojnacki, Cezary, Tomasz Popławski, Jan Chojnacki, Michał Fila, Paulina Konrad, and Janusz Blasiak. "Tryptophan Intake and Metabolism in Older Adults with Mood Disorders." Nutrients 12, no. 10 (October 18, 2020): 3183. http://dx.doi.org/10.3390/nu12103183.

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The role of serotonin in the pathogenesis of depression is well-documented, while the involvement of other tryptophan (TRP) metabolites generated in the kynurenine pathway is less known. The aim of this study was to assess the intake and metabolism of TRP in elderly patients with mood disorders. Ninety subjects in three groups, 30 subjects each, were enrolled in this study: controls (healthy young adults, group I) and elderly individuals without (group II) or with (group III) symptoms of mild and moderate depression, as assessed by the Hamilton Depression Rating Scale (HAM-D) and further refer
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Kiluk, Małgorzata, Janina Lewkowicz, Dariusz Pawlak, and Anna Tankiewicz-Kwedlo. "Crosstalk between Tryptophan Metabolism via Kynurenine Pathway and Carbohydrate Metabolism in the Context of Cardio-Metabolic Risk—Review." Journal of Clinical Medicine 10, no. 11 (June 4, 2021): 2484. http://dx.doi.org/10.3390/jcm10112484.

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Scientific interest in tryptophan metabolism via the kynurenine pathway (KP) has increased in the last decades. Describing its metabolites helped to increase their roles in many diseases and disturbances, many of a pro-inflammatory nature. It has become increasingly evident that KP can be considered an important part of emerging mediators of diabetes mellitus and metabolic syndrome (MS), mostly stemming from chronic systemic low-grade inflammation resulting in the aggravation of cardiovascular complications. An electronic literature search of PubMed and Embase up to March 2021 was performed fo
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Vecchiarelli, Haley A., Chaitanya P. Gandhi, and Matthew N. Hill. "Acute Psychological Stress Modulates the Expression of Enzymes Involved in the Kynurenine Pathway throughout Corticolimbic Circuits in Adult Male Rats." Neural Plasticity 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/7215684.

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Tryptophan is an essential dietary amino acid that is necessary for protein synthesis, but also serves as the precursor for serotonin. However, in addition to these biological functions, tryptophan also serves as a precursor for the kynurenine pathway, which has neurotoxic (quinolinic acid) and neuroprotective (kynurenic acid) metabolites. Glucocorticoid hormones and inflammatory mediators, both of which are increased by stress, have been shown to bias tryptophan along the kynurenine pathway and away from serotonin synthesis; however, to date, there is no published data regarding the effects o
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Ciapała, Katarzyna, Joanna Mika, and Ewelina Rojewska. "The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives." International Journal of Molecular Sciences 22, no. 20 (October 13, 2021): 11055. http://dx.doi.org/10.3390/ijms222011055.

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Accumulating evidence suggests the key role of the kynurenine pathway (KP) of the tryptophan metabolism in the pathogenesis of several diseases. Despite extensive research aimed at clarifying the mechanisms underlying the development and maintenance of neuropathic pain, the roles of KP metabolites in this process are still not fully known. Although the function of the peripheral KP has been known for several years, it has only recently been acknowledged that its metabolites within the central nervous system have remarkable consequences related to physiology and behavior. Both the products and
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Tanaka, Bohár, and Vécsei. "Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism." Molecules 25, no. 3 (January 28, 2020): 564. http://dx.doi.org/10.3390/molecules25030564.

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Worldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to proposing several hypotheses of AD pathogenesis, finding a presence of positive feedback loops and additionally observing the disturbance of a branch of tryptophan metabolism, the kynurenine (KYN) pathway. Either causative or resultant of dementia, elevated levels of neurotoxic KYN metabolites are observed, potenti
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Naz, Bhat, Ståhl, Forsslund, Sköld, Wheelock, and Wheelock. "Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD." Metabolites 9, no. 10 (October 1, 2019): 212. http://dx.doi.org/10.3390/metabo9100212.

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Increased activity of indoleamine 2,3-dioxygenase (IDO) and tryptophan hydroxylase (TPH) have been reported in individuals with chronic obstructive pulmonary disease (COPD). We therefore investigated the effect of gender stratification upon the observed levels of tryptophan metabolites in COPD. Tryptophan, serotonin, kynurenine, and kynurenic acid were quantified in serum of never-smokers (n = 39), smokers (n = 40), COPD smokers (n = 27), and COPD ex-smokers (n = 11) by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). The individual metabolite associations with lung func
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Sutphin, George, Hope Dang, Luis Espejo, Raul Castro-Portuguez, Bradford Hull, Jeremy Meyers, Emily Turner, and Destiny DeNicola. "Targeting kynurenine metabolism to reduce inflammation and enhance stress response during aging." Innovation in Aging 5, Supplement_1 (December 1, 2021): 682. http://dx.doi.org/10.1093/geroni/igab046.2565.

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Abstract Aberrant kynurenine pathway metabolism is increasingly linked to aging and age-associated disease. Kynurenine metabolic activity increases with age and becomes dysregulated during various forms of age-associated pathology in humans. By manipulating one or more kynurenine pathway enzymes and metabolites, we have extended lifespan up to 40% in Caenorhabditis elegans. In particular, elevating physiological levels of the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) by directly supplementing 3HAA or inhibiting the enzyme 3HAA dioxygenase (HAAO) extends C. elegans lifespan
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Hartai, Zsuzsanna, Peter Klivenyi, Tamas Janaky, Botond Penke, Laszlo Dux, and Laszlo Vecsei. "Peripheral Kynurenine Metabolism in Focal Dystonia." Medicinal Chemistry 3, no. 3 (May 1, 2007): 285–88. http://dx.doi.org/10.2174/157340607780620707.

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REINHARD, J. F. "Pharmacological Manipulation of Brain Kynurenine Metabolism." Annals of the New York Academy of Sciences 1035, no. 1 (December 1, 2004): 335–49. http://dx.doi.org/10.1196/annals.1332.020.

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Kolodziej, Lukasz R., Ewa M. Paleolog, and Richard O. Williams. "Kynurenine metabolism in health and disease." Amino Acids 41, no. 5 (October 23, 2010): 1173–83. http://dx.doi.org/10.1007/s00726-010-0787-9.

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49

Braidy, Nady, and Ross Grant. "Kynurenine pathway metabolism and neuroinflammatory disease." Neural Regeneration Research 12, no. 1 (2017): 39. http://dx.doi.org/10.4103/1673-5374.198971.

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50

Fellendorf, Frederike T., Johanna M. Gostner, Melanie Lenger, Martina Platzer, Armin Birner, Alexander Maget, Robert Queissner, et al. "Tryptophan Metabolism in Bipolar Disorder in a Longitudinal Setting." Antioxidants 10, no. 11 (November 10, 2021): 1795. http://dx.doi.org/10.3390/antiox10111795.

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Immune-mediated inflammatory processes and oxidative stress are involved in the aetiopathogenesis of bipolar disorder (BD) and weight-associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found to be more active in BD, and associated with overweight/obesity. This study aimed to investigate tryptophan metabolism in BD compared to controls (C), stratified by weight classes, in a longitudinal setting, dependent on the incidence of BD episodes. Peripheral tryptophan, kynurenine, and neopterin
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