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"kynurenine pathway"

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https://www.readbyqxmd.com/read/29789640/alterations-in-serum-kynurenine-pathway-metabolites-in-individuals-with-high-neocortical-amyloid-%C3%AE-load-a-pilot-study
#1
Pratishtha Chatterjee, Kathryn Goozee, Chai K Lim, Ian James, Kaikai Shen, Kelly R Jacobs, Hamid R Sohrabi, Tejal Shah, Prita R Asih, Preeti Dave, Candice ManYan, Kevin Taddei, David B Lovejoy, Roger Chung, Gilles J Guillemin, Ralph N Martins
The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer's disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65-90 y, were categorised into NAL+ (n = 35) and NAL- (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEε4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL- participants were observed in females (kynurenine, p = 0...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29787958/altered-tryptophan-catabolite-concentrations-in-major-depressive-disorder-and-associated-changes-in-hippocampal-subfield-volumes
#2
Kelly Doolin, Kelly A Allers, Sina Pleiner, Andre Liesener, Chloe Farrell, Leonardo Tozzi, Erik O'Hanlon, Darren Roddy, Thomas Frodl, Andrew Harkin, Veronica O'Keane
BACKGROUND: Tryptophan depletion is a well-replicated biological finding in Major Depressive Disorder (MDD). The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme, indolamine 2,3 dioxygenase (IDO), have been implicated in the pathogenesis of depression. IDO expression is driven by inflammatory cytokines, providing a putative link between inflammation and neuropathology. This study examined circulating concentrations of C-reactive protein (CRP), plasma tryptophan, kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) and whole blood mRNA expression of IDO in patients with major depressive disorder (MDD) compared with healthy controls (HC)...
May 19, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29775873/psychosocial-stress-and-inflammation-driving-tryptophan-breakdown-in-children-and-adolescents-a-cross-sectional-analysis-of-two-cohorts
#3
Nathalie Michels, Gerard Clarke, Loreto Olavarria-Ramirez, Sonia Gómez-Martínez, Ligia Esperanza Díaz, Ascensión Marcos, Kurt Widhalm, Livia A Carvalho
BACKGROUND: Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group...
May 15, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29773836/novel-pathway-of-3-hydroxyanthranilic-acid-formation-in-limazepine-biosynthesis-reveals-evolutionary-relation-between-phenazines-and-pyrrolobenzodiazepines
#4
Magdalena Pavlikova, Zdenek Kamenik, Jiri Janata, Stanislav Kadlcik, Marek Kuzma, Lucie Najmanova
Natural pyrrolobenzodiazepines (PBDs) form a large and structurally diverse group of antitumour microbial metabolites produced through complex pathways, which are encoded within biosynthetic gene clusters. We sequenced the gene cluster of limazepines and proposed their biosynthetic pathway based on comparison with five available gene clusters for the biosynthesis of other PBDs. Furthermore, we tested two recombinant proteins from limazepine biosynthesis, Lim5 and Lim6, with the expected substrates in vitro...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29753195/effect-of-l-tryptophan-and-its-metabolites-on-food-passage-from-the-crop-in-chicks
#5
T Tachibana, Y Kadomoto, M S I Khan, R Makino, M A Cline
l-tryptophan (l-Trp), an essential amino acid, is well known as a precursor of 5-hydroxytryptamine (5-HT) and melatonin. In mammals, l-Trp itself has been reported to suppress gastric emptying in mammals. In addition, 5-HT and melatonin are found in the gastrointestinal tract and affect food passage from the digestive tract in mammals. While the function of these factors in mammals is documented, there is little knowledge on their function in the digestive tract of birds. Therefore, the purpose of the present study was to determine if l-Trp and its metabolites affect the crop emptying rate in chicks (Gallus gallus)...
March 16, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29734055/kynurenine-pathway-metabolic-balance-influences-microglia-activity-targeting-kynurenine-monooxygenase-to-dampen-neuroinflammation
#6
Allison M Garrison, Jennifer M Parrott, Arnulfo Tuñon, Jennifer Delgado, Laney Redus, Jason C O'Connor
Chronic stress or inflammation increases tryptophan metabolism along the kynurenine pathway (KP), and the generation of neuroactive kynurenine metabolites contributes to subsequent depressive-like behaviors. Microglia regulate KP balance by preferentially producing oxidative metabolites, including quinolinic acid. Research has focused on the interplay between cytokines and HPA axis-derived corticosteroids in regulating microglial activity and effects of KP metabolites directly on neurons; however, the potential role that KP metabolites have directly on microglial activity is unknown...
April 22, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29728648/salivary-kynurenic-acid-response-to-psychological-stress-inverse-relationship-to-cortical-glutamate-in-schizophrenia
#7
Joshua Chiappelli, Laura M Rowland, Francesca M Notarangelo, S Andrea Wijtenburg, Marian A R Thomas, Ana Pocivavsek, Aaron Jones, Krista Wisner, Peter Kochunov, Robert Schwarcz, L Elliot Hong
Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia...
April 18, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29725904/chronic-mild-stress-alters-kynurenine-pathways-changing-the-glutamate-neurotransmission-in-frontal-cortex-of-rats
#8
David Martín-Hernández, Hiram Tendilla-Beltrán, José L M Madrigal, Borja García-Bueno, Juan C Leza, Javier R Caso
Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs...
May 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29725029/sex-differences-in-hippocampal-memory-and-kynurenic-acid-formation-following-acute-sleep-deprivation-in-rats
#9
Annalisa M Baratta, Silas A Buck, Austin D Buchla, Carly B Fabian, Shuo Chen, Jessica A Mong, Ana Pocivavsek
Inadequate sleep is a prevalent problem within our society that can result in cognitive dysfunction. Elevations in kynurenic acid (KYNA), a metabolite of the kynurenine pathway (KP) of tryptophan degradation known to impact cognition, in the brain may constitute a molecular link between sleep loss and cognitive impairment. To test this hypothesis, we investigated the impact of 6 hours of sleep deprivation on memory and KP metabolism (brain and plasma) in male and female rats. Sleep-deprived males were impaired in a contextual memory paradigm, and both sexes were impaired in a recognition memory paradigm...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29705534/increasing-kynurenine-brain-levels-reduces-ethanol-consumption-in-mice-by-inhibiting-dopamine-release-in-nucleus-accumbens
#10
Pablo Giménez-Gómez, Mercedes Pérez-Hernández, María Dolores Gutiérrez-López, Rebeca Vidal, Cristina Abuin-Martínez, Esther O'Shea, María Isabel Colado
Recent research suggests that ethanol (EtOH) consumption behaviour can be regulated by modifying the kynurenine (KYN) pathway, although the mechanisms involved have not yet been well elucidated. To further explore the implication of the kynurenine pathway in EtOH consumption we inhibited kynurenine 3-monooxygenase (KMO) activity with Ro 61-8048 (100 mg/kg, i.p.), which shifts the KYN metabolic pathway towards kynurenic acid (KYNA) production. KMO inhibition decreases voluntary binge EtOH consumption and EtOH preference in mice subjected to "drinking in the dark" (DID) and "two-bottle choice" paradigms, respectively...
April 18, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29703752/reassignment-of-the-human-aldehyde-dehydrogenase-aldh8a1-aldh12-to-the-kynurenine-pathway-in-tryptophan-catabolism
#11
Ian Davis, Yu Yang, Daniel Wherritt, Aimin Liu
The kynurenine pathway is the primary route for L-tryptophan degradation in mammals. Intermediates and side products of this pathway are involved in immune response and neurodegenerative diseases. This makes the study of enzymes, especially those from mammalian sources, of the kynurenine pathway worthwhile. Recent studies on a bacterial version of an enzyme of this pathway, 2-aminomuconate semialdehyde (2-AMS) dehydrogenase (AMSDH), have provided a detailed understanding of the catalytic mechanism and identified residues conserved for muconate semialdehyde recognition and activation...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29694960/kynurenine-pathway-in-autism-spectrum-disorders-in-children
#12
Vesna Bryn, Robert Verkerk, Ola H Skjeldal, Ola Didrik Saugstad, Heidi Ormstad
BACKGROUND: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. METHODS: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46...
April 25, 2018: Neuropsychobiology
https://www.readbyqxmd.com/read/29693118/ido-decreases-glycolysis-and-glutaminolysis-by-activating-gcn2k-while-it-increases-fatty-acid-oxidation-by-activating-ahr-thus-preserving-cd4-t%C3%A2-cell-survival-and-proliferation
#13
Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Ioannis Stefanidis
It is generally hypothesized in the literature that indoleamine 2,3‑dioxygenase (IDO), by degrading L‑tryptophan along the kynurenine pathway, suppresses CD4+ T‑cell function by inducing apoptosis, inhibiting proliferation and promoting differentiation towards a regulatory phenotype. These effects are either accompanied or directly lead to alterations in cell metabolism. The present study evaluated the pathways that govern the effect of IDO on the utilization of the three main energy sources in CD4+ T‑cells...
July 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29683396/reduced-peripheral-availability-of-tryptophan-and-increased-activation-of-the-kynurenine-pathway-and-cortisol-correlate-with-major-depression-and-suicide
#14
Amel Messaoud, Mensi Rym, Wahiba Douki, Fadoua Neffati, Mohamed Fadhel Najjar, Gabriella Gobbi, Flavia Valtorta, Lotfi Gaha, Stefano Comai
OBJECTIVES: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of tryptophan and indoleamino 2,3-dioxygenase (TDO, IDO) enzymes has not been yet clarified in MDD with or without suicidal behaviors. METHODS: We analyzed peripheral markers of Trp via 5-HT and Kyn pathways, Kyn/Trp ratio as a measure of TDO/IDO activities, cortisol, and psychopathology in 73 non-suicidal and 56 suicidal MDD patients, and in 40 healthy controls...
April 23, 2018: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/29682508/a-three-ring-circus-metabolism-of-the-three-proteogenic-aromatic-amino-acids-and-their-role-in-the-health-of-plants-and-animals
#15
REVIEW
Anutthaman Parthasarathy, Penelope J Cross, Renwick C J Dobson, Lily E Adams, Michael A Savka, André O Hudson
Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29677366/the-absence-of-indoleamine-2-3-dioxygenase-inhibits-retinal-capillary-degeneration-in-diabetic-mice
#16
Rooban B Nahomi, Sruthi Sampathkumar, Angela M Myers, Lynda Elghazi, Dawn G Smith, Jie Tang, C Allen Lee, Timothy S Kern, Ram H Nagaraj, Patrice E Fort
Purpose: Loss of retinal capillary endothelial cells and pericytes through apoptosis is an early event in diabetic retinopathy (DR). Inflammatory pathways play a role in early DR, yet the biochemical mechanisms are poorly understood. In this study, we investigated the role of indoleamine 2,3-dioxygenase (IDO), an inflammatory cytokine-inducible enzyme, on retinal endothelial apoptosis and capillary degeneration in the diabetic retina. Methods: IDO was detected in human and mouse retinas by immunohistochemistry or Western blotting...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29667084/investigation-of-the-aryl-hydrocarbon-receptor-and-the-intrinsic-tumoral-component-of-the-kynurenine-pathway-of-tryptophan-metabolism-in-primary-brain-tumors
#17
Anthony R Guastella, Sharon K Michelhaugh, Neil V Klinger, Hassan A Fadel, Sam Kiousis, Rouba Ali-Fehmi, William J Kupsky, Csaba Juhász, Sandeep Mittal
INTRODUCTION: There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment. METHODS: We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), as well as, the aryl hydrocarbon receptor (AhR), a carcinogenic transcription factor activated by KP metabolites...
April 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29608993/kynurenine-pathway-in-depression-a-systematic-review-and-meta-analysis
#18
REVIEW
Kamiyu Ogyu, Kaoruhiko Kubo, Yoshihiro Noda, Yusuke Iwata, Sakiko Tsugawa, Yuki Omura, Masataka Wada, Ryosuke Tarumi, Eric Plitman, Sho Moriguchi, Takahiro Miyazaki, Hiroyuki Uchida, Ariel Graff-Guerrero, Masaru Mimura, Shinichiro Nakajima
Abnormalities of the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression. However, the relationships between depression and each metabolite of the KYN pathway remain uncertain. Therefore, we conducted a meta-analysis about the levels of the metabolites of KYN pathway between patients with depression and controls. Out of 899 initial records, we identified 22 articles to form the empirical basis. Seventeen, 10, and 18 studies examined levels of kynurenic acid (KYNA), quinolinic acid (QUIN), and KYN, respectively...
March 30, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29607498/1-l-mt-an-ido-inhibitor-prevented-colitis-associated-cancer-by-inducing-cdc20-inhibition-mediated-mitotic-death-of-colon-cancer-cells
#19
Xiuting Liu, Wei Zhou, Xin Zhang, Yang Ding, Qianming Du, Rong Hu
Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29570959/galantamine-memantine-combination-for-cognitive-impairments-due-to-electroconvulsive-therapy-traumatic-brain-injury-and-neurologic-and-psychiatric-disorders-kynurenic-acid-and-mismatch-negativity-target-engagement
#20
Maju Mathew Koola
Cognitive impairments due to electroconvulsive therapy (ECT), traumatic brain injury (TBI), and neurologic and psychiatric disorders are prevalent. Cholinergic and glutamatergic pathways, α-7 nicotinic acetylcholine (α-7nACh) receptor, and N-methyl-d-aspartate (NMDA) receptor are potential pathophysiologic mechanisms in all of these conditions. Galantamine not only is an acetylcholinesterase inhibitor but has a dual mode of action as a α-7nACh receptor modulator as well. Memantine is a noncompetitive NMDA receptor antagonist...
March 1, 2018: Primary Care Companion to CNS Disorders
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