The kynurenine pathway and neurodegenerative disease

Huntington's disease: from molecular pathogenesis to clinical treatment

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Quinolinic Acid: An Endogenous Metabolite That Produces Axon-Sparing Lesions in Rat Brain

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An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid

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The Brain Metabolite Kynurenic Acid Inhibits α7 Nicotinic Receptor Activity and Increases Non-α7 Nicotinic Receptor Expression: Physiopathological Implications

Hilmas, C., Pereira, E., Alkondon, M., Rassoulpour, A., Schwarcz, R., & Albuquerque, E. X. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07463.2001 · Cited by 772 · see citing works

Blood–Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism

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Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset

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Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS

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QUINOLINIC ACID AND KYNURENINE PATHWAY METABOLISM IN INFLAMMATORY AND NON-INFLAMMATORY NEUROLOGICAL DISEASE

Heyes, M. P., Saito, K., Crowley, J. S., DAVIS, L. E., Demitrack, M. A., Der, M. G., Dilling, L. A., Elia, J., Kruesi, M. J. P., Lackner, A. A., et al. (1992) · Brain · doi:10.1093/brain/115.5.1249 · Cited by 682 · see citing works

A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease

Björkqvist, M., Wild, E. J., Thiele, J., Silvestroni, A., André, R., Lahiri, N., Raibon, E., Lee, R. V., Benn, C., Soulet, D., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080178 · Cited by 646 · see citing works

Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection

Guillemin, G. J., Kerr, S. J., Smythe, G. A., Smith, D. G., Kapoor, V., Armati, P. J., Croitoru‐Lamoury, J., & Brew, B. J. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00498.x · Cited by 541 · see citing works

Kynurenine 3-Monooxygenase Inhibition in Blood Ameliorates Neurodegeneration

Zwilling, D., Huang, S., Sathyasaikumar, K. V., Notarangelo, F. M., Guidetti, P., Wu, H., Lee, J. H., Truong, J. K., Andrews-Zwilling, Y. S., Hsieh, E., et al. (2011) · Cell · doi:10.1016/j.cell.2011.05.020 · Cited by 519 · see citing works

Mechanism of interferon-gamma action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity.

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3‐Hydroxykynurenine, an Endogenous Oxidative Stress Generator, Causes Neuronal Cell Death with Apoptotic Features and Region Selectivity

Okuda, S., Nishiyama, N., Saitō, H., & Katsuki, H. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70010299.x · Cited by 465 · see citing works

Microglial activation in presymptomatic Huntington's disease gene carriers

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NMDA Receptor Blockade by Ketamine Abrogates Lipopolysaccharide-Induced Depressive-Like Behavior in C57BL/6J Mice

Walker, A. K., Budac, D. P., Bisulco, S., Lee, A. W., Smith, R. A., Beenders, B., Kelley, K. W., & Dantzer, R. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.71 · Cited by 432 · see citing works

Kynurenines in CNS disease: regulation by inflammatory cytokines.

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Interleukin-1β: A New Regulator of the Kynurenine Pathway Affecting Human Hippocampal Neurogenesis

Zunszain, P. A., Anacker, C., Cattaneo, A., Choudhury, S., Musaelyan, K., Myint, A. M., Thuret, S., Price, J., & Pariante, C. M. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.277 · Cited by 388 · see citing works

Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro

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On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress

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Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases.

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Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus

Guillemin, G., Brew, B., Noonan, C. E., Takikawa, O., & Cullen, K. (2005) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2005.00655.x · Cited by 331 · see citing works

A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease

Giorgini, F., Guidetti, P., Nguyen, Q., Bennett, S. C., & Muchowski, P. J. (2005) · Nature Genetics · doi:10.1038/ng1542 · Cited by 325 · see citing works

Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes

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l-Kynurenine Its synthesis and possible regulatory function in brain

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Kynurenine pathway abnormalities in Parkinson's disease

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Tryptophan metabolism and oxidative stress in patients with Huntington's disease

Stoy, N., Mackay, G. M., Forrest, C., Christofides, J., Egerton, M., Stone, T., & Darlington, L. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03070.x · Cited by 315 · see citing works

Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.

Okuda, S., Nishiyama, N., Saitō, H., & Katsuki, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12553 · Cited by 302 · see citing works

Kynurenine and its metabolites in Alzheimer's disease patients

Gulaj, E., Pawlak, K., Bień, B., & Pawlak, D. (2010) · Advances in Medical Sciences · doi:10.2478/v10039-010-0023-6 · Cited by 289 · see citing works

Quinolinic acid is a potent lipid peroxidant in rat brain homogenates

Rı́os, C., & Santamarı́a, A. (1991) · Neurochemical Research · doi:10.1007/bf00966592 · Cited by 272 · see citing works

The Kynurenine Pathway Modulates Neurodegeneration in a Drosophila Model of Huntington's Disease

Campesan, S., Green, E. W., Breda, C., Sathyasaikumar, K. V., Muchowski, P. J., Schwarcz, R. M., Kyriacou, C. P., & Giorgini, F. (2011) · Current Biology · doi:10.1016/j.cub.2011.04.028 · Cited by 261 · see citing works

Neostriatal and cortical quinolinate levels are increased in early grade Huntington's disease

GUIDETTI, P., Luthi‐Carter, R., Augood, S. J., & Schwarcz, R. M. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.07.006 · Cited by 259 · see citing works

The Excitotoxin Quinolinic Acid Induces Tau Phosphorylation in Human Neurons

Rahman, A., Ting, K., Cullen, K. M., Braidy, N., Brew, B. J., & Guillemin, G. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006344 · Cited by 257 · see citing works

Mechanism for Quinolinic Acid Cytotoxicity in Human Astrocytes and Neurons

Braidy, N., Grant, R., Adams, S., Brew, B., & Guillemin, G. (2009) · Neurotoxicity research · doi:10.1007/s12640-009-9051-z · Cited by 234 · see citing works

Expression of The Kynurenine Pathway Enzymes in Human Microglia and Macrophages

Guillemin, G. J., Smith, D. G., Smythe, G. A., Armati, P. J., & Brew, G. J. (2003) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4615-0135-0_12 · Cited by 229 · see citing works

Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl

Behan, W. M. H., McDonald, M., Darlington, L. G., & Stone, T. W. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702940 · Cited by 225 · see citing works

Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: A role for IFN-γ?

Connor, T. J., Starr, N., O’Sullivan, J. B., & Harkin, A. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.06.007 · Cited by 213 · see citing works

Synthesis and Biochemical Evaluation ofN-(4-Phenylthiazol-2-yl)benzenesulfonamides as High-Affinity Inhibitors of Kynurenine 3-Hydroxylase

Röver, S., Cesura, A. M., Huguenin, P. N., Kettler, R., & Szente, A. (1997) · Journal of Medicinal Chemistry · doi:10.1021/jm970467t · Cited by 212 · see citing works

3-Hydroxykynurenine and 3-Hydroxyanthranilic Acid Generate Hydrogen Peroxide and Promote α-Crystallin Cross-Linking by Metal Ion Reduction

Goldstein, L. E., Leopold, M. C., Huang, X., Atwood, C., Saunders, A. J., Hartshorn, M. A., Lim, J. T., Faget, K. Y., Muffat, J., Scarpa, R. C., et al. (2000) · Biochemistry · doi:10.1021/bi992997s · Cited by 212 · see citing works

Distinct neuroinflammatory profile in post-mortem human Huntington's disease

Silvestroni, A., Faull, R. L. M., Strand, A. D., & Möller, T. (2009) · Neuroreport · doi:10.1097/wnr.0b013e32832e34ee · Cited by 204 · see citing works

On the excitotoxic properties of quinolinic acid, 2,3-piperidine dicarboxylic acids and structurally related compounds

Foster, A. C. (1983) · Neuropharmacology · doi:10.1016/0028-3908(83)90221-6 · Cited by 194 · see citing works

Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice

Lapin, I. P. (1978) · Journal of Neural Transmission · doi:10.1007/bf01262727 · Cited by 193 · see citing works

Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

de la Cruz, V. P., Carrillo-Mora, P. U., & Santamarı́a, A. (2012) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s8158 · Cited by 193 · see citing works

Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

van der Goot, A. T., Zhu, W., Vázquez‐Manrique, R. P., Seinstra, R. I., Dettmer, K., Michels, H., Farina, F., Krijnen, J., Melki, R., Buijsman, R. C., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203083109 · Cited by 192 · see citing works

3‐Hydroxykynurenine potentiates quinolinate but not NMDA toxicity in the rat striatum

Guidetti, P., & Schwarcz, R. M. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00806.x · Cited by 180 · see citing works

Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system

Whetsell, W. O., & Schwarcz, R. M. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90609-5 · Cited by 176 · see citing works

Increased neopterin production and tryptophan degradation in advanced Parkinson's disease.

Widner, B., Leblhuber, F., & Fuchs, D. (2002) · Journal of Neural Transmission · doi:10.1007/s007020200014 · Cited by 171 · see citing works

A mechanism of quinolinic acid formation by brain in inflammatory neurological disease: Attenuation of synthesis from L-tryptophan by 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate

Heyes, M. P., Saito, K., Major, E. O., Milstien, S., Markey, S. P., & Vickers, J. H. (1993) · Brain · doi:10.1093/brain/116.6.1425 · Cited by 171 · see citing works

Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice

Guidetti, P., Bates, G. P., Graham, R. K., Hayden, M. R., Leavitt, B. R., MacDonald, M. E., Slow, E., Wheeler, V. C., Woodman, B., & Schwarcz, R. M. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.02.011 · Cited by 166 · see citing works

Effect of quinolinic acid on human astrocytes morphology and functions: implications in Alzheimer's disease

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Increased 3-Hydroxykynurenine serum concentrations differentiate Alzheimer’s disease patients from controls

Schwarz, M., Guillemin, G. J., Teipel, S. J., Büerger, K., & Hampel, H. J. (2012) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-012-0384-x · Cited by 141 · see citing works

Aβ1-42 induces production of quinolinic acid by human macrophages and microglia

Guillemin, G. J., Smythe, G. A., Veas, L. A., Takikawa, O., & Brew, B. J. (2003) · Neuroreport · doi:10.1097/00001756-200312190-00005 · Cited by 137 · see citing works

Targeted Deletion of Kynurenine 3-Monooxygenase in Mice

Giorgini, F., Huang, S.-Y., Sathyasaikumar, K. V., Notarangelo, F. M., Thomas, M. A. R., Tararina, M. A., Wu, H., Schwarcz, R. M., & Muchowski, P. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.503813 · Cited by 131 · see citing works

Structural basis of kynurenine 3-monooxygenase inhibition

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Targets for future clinical trials in Huntington's disease: What's in the pipeline?

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MK-801, an receptor antagonist, blocks quinolinic acid-induced lipid peroxidation in rat corpus striatum

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Dysfunction of brain kynurenic acid metabolism in Huntington's disease: focus on kynurenine aminotransferases

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Synthesis of Quinolinic Acid by 3‐Hydroxyanthranilic Acid Oxygenase in Rat Brain Tissue In Vitro

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Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease

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Importance of the Two Interferon-stimulated Response Element (ISRE) Sequences in the Regulation of the Human Indoleamine 2,3-Dioxygenase Gene

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Uptake of Kynurenine into Rat Brain Slices

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Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine

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Brain‐Specific Modulation of Kynurenic Acid Synthesis in the Rat

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In vitro evidence for an antioxidant role of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in the brain.

Leipnitz, G., Schumacher, C., Dalcin, K. B., Scussiato, K., Solano, A., Funchal, C., Dutra-filho, C., Wyse, A., Wannmacher, C., Latini, A., et al. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2006.04.017 · Cited by 104 · see citing works

Quinolinic acid — Iron(II) complexes: Slow autoxidation, but enhanced hydroxyl radical production in the Fenton reaction

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Histone Deacetylase Inhibition Modulates Kynurenine Pathway Activation in Yeast, Microglia, and Mice Expressing a Mutant Huntingtin Fragment

Giorgini, F., Möller, T., Kwan, W., Zwilling, D., Wacker, J. L., Hong, S. Y., Tsai, L. L., Cheah, C. S., Schwarcz, R. M., Guidetti, P., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708192200 · Cited by 97 · see citing works

The effect of quinolinate on rat brain lipid peroxidation is dependent on iron

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Electrochemical and in vitro evaluation of the redox-properties of kynurenine species

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Characterisation of the major autoxidation products of 3-hydroxykynurenine under physiological conditions

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Antioxidant treatment protects striatal neurons against excitotoxic insults

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The IDO Inhibitor Coptisine Ameliorates Cognitive Impairment in a Mouse Model of Alzheimer's Disease

Yu, D., Tao, B.-B., Yang, Y.-Y., Du, L., Yang, S.-S., He, X.-J., Zhu, Y., Yan, J., & Yang, Q. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-140414 · Cited by 88 · see citing works

Oren-gedoku-to and its Constituents with Therapeutic Potential in Alzheimer's Disease Inhibit Indoleamine 2, 3-Dioxygenase Activity In Vitro

Yu, C.-J., Zheng, M., Kuang, C., Huang, W., & Yang, Q. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100684 · Cited by 85 · see citing works

Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase.

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Blood levels of kynurenines, interleukin‐23 and soluble human leucocyte antigen‐G at different stages of Huntington’s disease

Forrest, C., Mackay, G. M., Stoy, N., Spiden, S. L., Taylor, R., Stone, T. W., & Darlington, L. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06442.x · Cited by 83 · see citing works

Quinolinic acid phosphoribosyltransferase in human and rat brain: Activity in Huntington's disease and in quinolinate-lesioned rat striatum

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Tissue expression and biochemical characterization of human 2‐amino 3‐carboxymuconate 6‐semialdehyde decarboxylase, a key enzyme in tryptophan catabolism

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Heme: A Regulator of Rat Hepatic Tryptophan 2,3-Dioxygenase?

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DYSFUNCTIONAL KYNURENINE PATHWAY METABOLISM IN THE R6/2 MOUSE MODEL OF HUNTINGTON’S DISEASE

Sathyasaikumar, K. V., Stachowski, E. K., Amori, L., Guidetti, P., Muchowski, P., & Schwarcz, R. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06675.x · Cited by 72 · see citing works

Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway.

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Nitric oxide synthase inhibition prevents acute quinolinate-induced striatal neurotoxicity

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Structural and functional analyses of human tryptophan 2,3-dioxygenase

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Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

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Proinflammatory cytokine interferon‐γ increases induction of indoleamine 2,3‐dioxygenase in monocytic cells primed with amyloid β peptide 1–42: implications for the pathogenesis of Alzheimer’s disease

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5-Hydroxyanthranilic Acid, a Tryptophan Metabolite, Generates Oxidative Stress and Neuronal Death via p38 Activation in Cultured Cerebellar Granule Neurones

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