The kynurenine pathway in neurodegenerative diseases: Mechanistic and therapeutic considerations

Journal of the Neurological Sciences

Volumn 323, Issue 1-2, 2012, Pages 1-8

  Tan, Lin ^a   Yu, Jin Tai ^a,b   Tan, Lan ^a,b  

^a QINGDAO UNIVERSITY   (China)

^b OCEAN UNIVERSITY OF CHINA   (China)

Author keywords

Aging; Alzheimer's disease (AD); Amyotrophic lateral sclerosis (ALS); Huntington's disease (HD); Kynurenine pathway; Parkinson's disease (PD)

Indexed keywords

2 (2 N,N DIMETHYLAMINOETHLAMINE 1 CARBONYL) 1H QUINOLIN 4 ONE HYDROCHLORIDE; 3 HYDROXYKYNURENINE; 3,4 DIMETHOXY N [4 (3 NITROPHENYL) 2 THIAZOLYL]BENZENESULFONAMIDE; ANTIPARKINSON AGENT; CENTRAL NERVOUS SYSTEM AGENTS; CHINESE DRUG; DIZOCILPINE; DONEPEZIL; DOPAMINE RECEPTOR STIMULATING AGENT; ENZYME INHIBITOR; GALANTAMINE; INDUCIBLE NITRIC OXIDE SYNTHASE; KYNURENIC ACID; KYNURENIC ACID DERIVATIVE; KYNURENINE; KYNURENINE AMINOTRANSFERASE; LEVODOPA; MEMANTINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NICOTINYLALANINE; OXYGENASE INHIBITOR; PICOLINIC ACID; PLATINUM DICHLOROBIS(ISOPROPYLAMINE); PROBENECID; QUINOLINIC ACID; RIVASTIGMINE; SEROTONIN; TRYPTOPHAN; UNCLASSIFIED DRUG; UNINDEXED DRUG; UPF 648;

ALZHEIMER DISEASE; AMINO ACID METABOLISM; AMYLOID PLAQUE; AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; ARTICLE; BLOOD BRAIN BARRIER; DEMENTIA; DNA FRAGMENTATION; DOPAMINERGIC NERVE CELL; EXCITOTOXICITY; GENE MUTATION; HUMAN; HUNTINGTON CHOREA; LEWY BODY; NEUROFIBRILLARY TANGLE; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; UNSPECIFIED SIDE EFFECT;

EID: 84867864051     PISSN: 0022510X     EISSN: 18785883     Source Type: Journal    
DOI: 10.1016/j.jns.2012.08.005     Document Type: Review

References (76)

1. V. Pérez-De La Cruz, M. Königsberg, and A. Santamaría Kynurenine pathway and disease: an overview CNS Neurol Disord Drug Targets 6 2007 398 410
2. N. Braidy, R. Grant, B.J. Brew, S. Adams, T. Jayasena, and G.J. Guillemin Effects of kynurenine pathway metabolites on intracellular NAD + synthesis and cell death in human primary astrocytes and neurons Int J Tryptophan Res 2 2009 61 69
3. D. Meininger, L. Zalameda, Y. Liu, L.P. Stepan, L. Borges, and J.D. McCarter Purification and kinetic characterization of human indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) and discovery of selective IDO1 inhibitors Biochim Biophys Acta 1814 2011 1947 1954
4. D. Zadari, P. Klivenyi, E. Vamos, F. Fulop, J. Toldi, and L. Vecsei Kynurenines in chronic neurodegenerative disorders: future therapeutic strategies J Neural Transm 116 2009 1403 1409
5. Xiao-Dan Wang, F.M. Notarangelo, J.Z. Wang, and R. Schwarcz Kynurenic acid and 3-hydroxykynurenine production from d-kynurenine in mice Brain Res 1455 2012 1 9
6. L. Asp, A.S. Johansson, A. Mann, B. Owe-Larsson, E.M. Urbanska, and T. Kocki Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts J Inflamm 8 2011 25
7. E. Vamos, A. Pardutz, P. Klivenyi, J. Toldi, and L. Vecsei The role of kynurenines in disorders of the central nervous system: possibilities for neuroprotection J Neurol Sci 283 2009 21 27
8. R. Lugo-Huitron, T. Blanco-Ayala, P. Ugalde-Muniz, P. Carrillo-Mora, J. Pedraza-Chaverri, and D. Silva-Adaya On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress Neurotoxicol Teratol 33 2011 538 547
9. K. Sas, H. Robotka, J. Toldi, and L. Vecsei Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders J Neurol Sci 257 2007 221 239
10. D. Krause, H.S. Suh, L. Tarassishin, Q.L. Cui, B.A. Durafourt, and A. Bauman The tryptophan metabolite 3-hydroxyanthranilic acid plays anti-inflammatory and neuroprotective roles during inflammation: role of hemeoxygenase-1 Am J Pathol 179 2011 1360 1372
11. P.F. Schuck, A. Tonin, G. da Costa Ferreira, C.M. vViegas, A. Latini, and C.M. Duval Wannmacher Kynurenines impair energy metabolism in rat cerebral cortex Cell Mol Neurobiol 27 2007 147 160
12. G.F. Oxenkrug Interferon-gamma-inducible kynurenines/pteridines inflammation cascade: implications for aging and aging-associated psychiatric and medical disorders J Neural Transm 118 2011 75 85
13. P.H. Reinhart, and J.W. Kelly Treating the periphery to ameliorate neurodegenerative diseases Cell 145 2011 813 814
14. F. Fazio, L. Lionetto, G. Molinaro, H.O. Bertrand, F. Acher, and R.T. Ngomba Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type-4 metabotropic glutamate receptors Mol Pharmacol 81 2012 643 656
15. G.F. Oxenkrug Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism Ann N Y Acad Sci 1199 2010 1 14
16. B. Frick, K. Schroecksnadel, G. Neurauter, F. Leblhuber, and D. Fuchs Increasing production of homocysteine and neopterin and degradation of tryptophan with older age Clin Biochem 37 2004 684 687
17. H. Miura, N. Ozaki, T. Shirokawa, and K. Isobe Changes in brain tryptophan metabolism elicited by aging, social environment, and psychological stress in mice Stress 11 2008 160 169
18. A. Párdutz, A. Fejes, Z. Bohár, L. Tar, J. Toldi, and L. Vécsei Kynurenines and headache J Neural Transm 119 2012 285 296
19. T. Kocki, S. Wnuk, R. Kloc, J. Kocki, B. Owe-Larsson, and E.M. Urbanska New insight into the antidepressants action: modulation of kynurenine pathway by increasing the kynurenic acid/3-hydroxykynurenine ratio J Neural Transm 119 2012 235 243
20. M. Kanai, H. Funakoshi, H. Takahashi, T. Hayakawa, S. Mizuno, and K. Matsumoto Tryptophan 2, 3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice Mol Brain 2 2009 8
21. N. Braidy, G.J. Guillemin, H. Mansour, T. Chan-Ling, and R. Grant Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats FEBS J 278 2011 4425 4434
22. G.F. Oxenkrug Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging Ann N Y Acad Sci 1122 2007 35 49
23. 2-microglobulin changes Neurosignals 14 2005 126 135
24. M. Alkondon, E.F. Pereira, H.M. Eisenberg, Y. Kajii, R. Schwarcz, and E.X. Albuquerque Age dependency of inhibition of 7 nicotinic receptors and tonically active N-methyl-d-aspartate receptors by endogenously produced kynurenic acid in the brain J Parmacol Exp Ther 337 2011 572 582
25. I. Plangar, D. Zádori, P. Klivényi, J. Toldi, and L. Vécsei Targeting the kynurenine pathway-related alterations in Alzheimer's disease: a future therapeutic strategy J Alzheimers Dis 24 2011 199 209
26. K.K. Ting, B. Brew, and G. Guillemin The involvement of astrocytes and kynurenine pathway in Alzheimer's disease Neurotox Res 12 2007 247 262
27. A. Yamada, H. Akimoto, S. Kagawa, G.J. Guillemin, and O. Takikawa Proinflammatory cytokine interferon- 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 J Neurochem 110 2009 791 800
28. D.J. Bonda, M. Mailankot, J.G. Stone, M.R. Garrett, M. Staniszewska, and R.J. Castellani Indoleamine 2, 3-dioxygenase and 3-OH-kynurenine modifications are found in the neuropathology of Alzheimer Disease Redox Rep 15 4 2010 161 168
29. E. Gulaj, K. Pawlak, B. Bien, and D. Pawlak Kynurenine and its metabolites in Alzheimer's disease patients Adv Med Sci 55 2010 204 211
30. Z.T. Kincses, J. Toldi, and L. Vécsei Kynurenines, neurodegeneration and Alzheimer's disease J Cell Mol Med 14 2010 2045 2054
31. S.E. Coggan, G.A. Smythe, A. Bilgin, and R.S. Grant Age and circadian influences on picolinic acid concentrations in human cerebrospinal fluid J Neurochem 108 2009 1220 1225
32. Z. Hartai, A. Juhász, A. Rimanóczy, T. Janáky, T. Donkó, and L. Dux Decreased serum and red blood cell kynurenic acid levels in Alzheimer's disease Neurochem Int 50 2007 308 313
33. F. Rossi, R. Schwarz, and M. Rizzi Curiosity to kill the KAT (kynurenine aminotransferase):structural insights into brain kynurenic acid synthesis Curr Opin Struct Biol 18 2008 748 755
34. D. Zwilling, S.Y. Huang, K.V. Sathyasaikumar, F.M. Notarangelo, P. Guidetti, and H.Q. Wu Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration Cell 145 2011 863 874
35. C.J. Yu, M.F. Zheng, C.X. Kuang, W.D. Huang, and Q. Yang Oren-gedoku-to and its constituents with therapeutic potential in Alzheimer's disease inhibit indoleamine 2, 3-dioxygenase activity in vitro J Alzheimer's Dis 22 2010 257 266
36. P. Carrillo-Mora, L.A. Méndez-Cuesta, V. Pérez-De La Cruz, T.I. Fortoul-van Der Goes, and A. Santamaría Protective effect of systemic l-kynurenine and probenecid administration on behavioural and morphological alterations induced by toxic soluble amyloid beta (25-35) in rat hippocampus Behav Brain Res 210 2010 240 250
37. C.Y. Gong, Z. Li, H.M. Wang, J. Liu, L. Chen, and H.W. Zhang Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease Med Hypotheses 77 2011 383 385
38. G. Gárdián, and L. Vécsei Medical treatment of Parkinson's disease: today and the future J Clin Pharmacol Ther 48 2010 633 642
39. W.M. Caudle, and J. Zhang Glutamate, excitotoxicity and programmed cell death in Parkinson disease Exp Neurol 3 2009 220 230
40. N. Szabo, Z.T. Kincses, J. Toldi, and L. Vécsei Altered tryptophan metabolism in Parkinson's disease: a possible novel therapeutic approach J Neurol Sci 310 2011 256 260
41. D. Zadori, P. Klivényi, I. Plangár, J. Toldi, and L. Vécsei Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines J Cell Mol Med 15 2011 701 717
42. A. Zinger, C. Barcia, M.T. Herrero, and G.J. Guillemin The involvement of neuroinflammation and kynurenine pathway in Parkinson's disease Park Dis 2011 716859
43. Z. Hartai, P. Klivenyi, T. Janaky, B. Penke, L. Dux, and L. Vecsei Kynurenine metabolism in plasma and in red blood cells in Parkinson's disease J Neurol Sci 239 2005 31 35
44. E. Knyihar-Csillik, Z. Chadaide, A. Mihály, B. Krisztin-Péva, R. Fenyo, and L. Vécsei Effect of 6-hydroxydopamine treatment on kynurenine aminotransferase-I (KAT-I) immunoreactivity of neurons and glial cells in the rat substantia nigra Acta Neuropathol 112 2006 127 137
45. Y. Lee do, K.S. Lee, H.J. Lee, Y.H. Noh, H. Kim do, and J.Y. Lee Kynurenic acid attenuates MPP+-induced dopaminergic neuronal cell death via a Bax-mediated mitochondrial pathway Eur J Cell Biol 87 2008 389 397
46. P. Guidetti, G.P. Bates, R.K. Graham, M.R. Hayden, B.R. Leavitt, and M.E. MacDonald Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington's disease mice Neurobiol Dis 23 2006 190 197
47. D. Zádori, P. Klivényi, J. Toldi, F. Fülöp, and L. Vécsei Kynurenines in Parkinson's disease: therapeutic perspectives J Neural Transm 119 2012 275 283
48. H. Németh, J. Toldi, and L. Vécsei Kynurenines, Parkinson's disease and other neurodegenerative disorders: preclinical and clinical studies J Neural Transm Suppl 70 2006 285 304
49. E. Vamos, K. Voros, D. Zadori, L. Vecsei, and P. Klivenyi Neuroprotective effects of probenecid in a transgenic animal model of Huntington's disease J Neural Transm 116 2009 1079 1086
50. D. Silva-Adava, V. Pérez-De La Cruz, J. Villeda-Hernández, P. Carrillo-Mora, I.G. González-Herrera, and E. García Protective effect of l-kynurenine and probenecid on 6-hydroxydopamine-induced striatal toxicity in rats: implications of modulating kynurenate as a protective strategy Neurotoxicol Teratol 33 2011 303 312
51. M. Marosi, D. Nagy, T. Farkas, Z. Kis, E. Rózsa, and H. Robotka A novel kynurenic acid analogue: a comparison with kynurenic acid: an electrophysiological study J Neural Transm 117 2010 183 188
52. P. Klivenyi, and L. Vecsei Novel therapeutic strategies in Parkinson's disease Eur J Clin Pharmacol 66 2010 119 125
53. L. Amori, P. Guidetti, R. Pellicciari, Y. Kajii, and R. Schwarcz On the relationship between the two branches of the kynurenine pathway in the rat brain in vivo J Neurochem 109 2009 316 325
54. K. Sas, H. Robotka, J. Toldi, and L. Vécsei Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders J Neurol Sci 257 2007 221 239
55. S. Campesan, Green Ew, C. Breda, K.V. Sathyasaikumar, P.J. Muchowski, and R. Schwarcz The kynurenine pathway modulates neurodegeneration in a drosophila model of Huntington's disease Curr Biol 21 2011 961 966
56. V. Perez-De La Cruz, and A. Santamaria Integrative hypothesis for Huntington's disease: a brief review of experimental evidence Physiol Res 56 2007 513 526
57. K.V. Santhyasaikumar, E.K. Stachowski, L. Amori, P. Guidetti, P.J. Muchowski, and R. Schwarcz Dysfunctional kynurenine pathway metabolism in the R6/2 mouse model of Huntington's disease J Neurochem 113 2010 1416 1425
58. M.A. Thevandavakkam, R. Schwarcz, P.J. Muchowski, and F. Giorgini Targeting kynurenine 3-monooxygenase (KMO): implications for therapy in Huntington's disease CNS Neurol Disord Drug Targets 9 2010 791 800
59. R. Schwarcz, P. Guidetti, K.V. Sathyasaikumar, and P.J. Muchowski Of mice, rats and men: revisiting the quinolinic acid hypothesis of Huntington's disease Prog Neurobiol 90 2010 230 245
60. P. Guidetti, R.E. Luthi-Carter, S.J. Augood, and R. Schwarcz Neostriatal and cortical quinolinate levels are increased in early grade Huntington's disease Neurobiol Dis 17 2004 Dec 455 461
61. M.M. Fan, and L.A. Raymond N-methyl-d-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease Prog Neurobiol 81 2007 272 293
62. F. Giorgini, P. Guidetti, Q. Nguyen, S.C. Bennett, and P.J. Muchowski A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease Nat Genet 37 2005 526 531
63. M.T. Sapko, P. Guidetti, P. Yu, D.A. Tagle, R. Pellicciari, and R. Schwarcz Endogenous kynurenate controls the vulnerability of strial neurons to quinolinate: implications for Huntington's disease Exp Neurol 197 2006 31 40
64. B. Poeggeler, A. Rassoulpour, H.Q. Wu, P. Guidetti, R.C. Roberts, and R. Schwarcz Dopamine receptor activation reveals a novel, kynurenate-sensitive component of striatal N-methyl-d-aspartate neurotoxicity Neuroscience 148 2007 188 197
65. D. Zadori, G. Nyiri, A. Szonyi, I. Szatmári, F. Fülöp, and J. Toldi Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse model of Huntington's disease J Neural Transm 118 2011 865 875
66. F. Glorgini, T. Möller, W. Kwan, D. Zwilling, J.L. Wacker, and S. Hong Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment J Biol Chem 283 2008 7390 7400
67. Y. Chen, V. Meininger, and G.J. Guillemin Recent advances in the treatment of amyotrophic lateral sclerosis: emphasis on kynurenine pathway inhibitors Cent Nerv Syst Agents Med Chem 9 2009 32 39
68. G.J. Gillemin, V. Meininger, and B.J. Brew Implications for the kynurenine pathway and quinolinic acid in amyotrophic lateral sclerosis Neurodegener Dis 2 2005 166 176
69. H. Zhang, C. Andrekopoulos, J. Joseph, K. Chandran, H. Karoui, and J.P. Crow Bicarbonate-dependent peroxidase activity of human Cu, Zn-superoxide dismutase induces covalent aggregation of protein: intermediacy of tryptophan-derived oxidation products J Biol Chem 278 2003 24078 24089
70. Y. Chen, R. Stankovic, K.M. Cullen, V. Meininger, B. Garner, and S. Coggan The kynurenine pathway and inflammation in amyotrophic lateral sclerosis Neurotox Res 18 2010 132 142
71. Y. Chen, B.J. Brew, and G.J. Guillemin Characterization of the kynurenine pathway in NSC-34 cell line: implications for amyotrophic lateral sclerosis J Neurochem 118 2011 816 825
72. B.J. Trayno, L. Bruijn, R. Conwit, F. Beal, G. O'Neill, and S.C. Fagan Neuroprotective agents for clinical trials in ALS: a systematic assessment Neurology 67 2006 20 27
73. N. Wszelaki, and M.F. Melzig Research on an in vitro cell system for testing the neurotoxicity of kynurenine pathway metabolites Pharmazie 66 2011 899 903
74. S. Erhardt, S.K. Olsson, and G. Engberg Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders CNS Drugs 23 2009 91 101
75. B.C. DiNatale, I.A. Murray, J.C. Schroeder, C.A. Flaveny, T.S. Lahoti, and E.M. Laurenzana Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling Toxicol Sci 115 2010 89 97
76. J. Wang, N. Simonavicius, X. Wu, G. Swaminath, J. Reagan, H. Tian, and L. Ling Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35 J Biol Chem 281 2006 22021 22028