Mitochondrial disturbances, excitotoxicity, neuroinflammation and kynurenines: Novel therapeutic strategies for neurodegenerative disorders

Journal of the Neurological Sciences

Volumn 322, Issue 1-2, 2012, Pages 187-191

  Zádori, Dénes ^a   Klivényi, Péter ^a   Szalárdy, Levente ^a   Fülöp, Ferenc ^b   Toldi, József ^c,d   Vécsei, László ^a,d  

^a UNIVERSITY OF SZEGED   (Hungary)

^b UNIVERSITY OF SZEGED   (Hungary)

^c UNIVERSITY OF SZEGED   (Hungary)

^d UNIVERSITY OF SZEGED   (Hungary)

Author keywords

Cerebral ischemia; Glutamate excitotoxicity; Huntington's disease; Kynurenic acid; Kynurenine system; Mitochondrial dysfunction; Neurodegeneration; Neuroinflammation

Indexed keywords

(M NITROBENZOYL)ALANINE; 2 (3,4 DIMETHOXYBENZENESULFONYLAMINO) 4 (3 NITROPHENYL) 5 (PIPERIDIN 1 YL)METHYLTHIAZOLE; 3 HYDROXYKYNURENINE; 3,4 DIMETHOXY N [4 (3 NITROPHENYL) 2 THIAZOLYL]BENZENESULFONAMIDE; 3,4 DIMETHOXY N [4 (NITROPHENYL)THIAZOL 2 YL]BENZENESULFONAMIDE; ALANINE DERIVATIVE; GLUTAMIC ACID; KYNURENINE; KYNURENINE AMINOTRANSFERASE; NICOTINYLALANINE; PROBENECID; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ADD ON THERAPY; ARTICLE; BRAIN ISCHEMIA; CAROTID ARTERY OBSTRUCTION; CLINICAL FEATURE; DEGENERATIVE DISEASE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG TARGETING; EXCITOTOXICITY; HUMAN; HUNTINGTON CHOREA; MEDICAL LITERATURE; NERVOUS SYSTEM INFLAMMATION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL;

ANIMALS; BRAIN ISCHEMIA; ENCEPHALITIS; HUMANS; HUNTINGTON DISEASE; KYNURENINE; MITOCHONDRIA;

EID: 84867582500     PISSN: 0022510X     EISSN: 18785883     Source Type: Journal    
DOI: 10.1016/j.jns.2012.06.004     Document Type: Article

References (72)

1. D. Zadori, P. Klivenyi, I. Plangar, J. Toldi, and L. Vecsei Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines J Cell Mol Med 15 2011 701 717
2. Y. Wang, H. Liu, G. McKenzie, P.K. Witting, J.P. Stasch, and M. Hahn Kynurenine is an endothelium-derived relaxing factor produced during inflammation Nat Med 16 2010 279 285
3. P.H. Chan Reactive oxygen radicals in signaling and damage in the ischemic brain J Cereb Blood Flow Metab 21 2001 2 14
4. K. Niizuma, H. Yoshioka, H. Chen, G.S. Kim, J.E. Jung, and M. Katsu Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia Biochim Biophys Acta 1802 2010 92 99
5. C. Iadecola Neurovascular regulation in the normal brain and in Alzheimer's disease Nat Rev Neurosci 5 2004 347 360
6. V.L. Dawson, T.M. Dawson, D.A. Bartley, G.R. Uhl, and S.H. Snyder Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures J Neurosci 13 1993 2651 2661
7. D.M. Ferriero, L.J. Arcavi, S.M. Sagar, T.K. McIntosh, and R.P. Simon Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia Ann Neurol 24 1988 670 676
8. Z.G. Zhang, M. Chopp, C. Zaloga, J.S. Pollock, and U. Forstermann Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats Stroke 24 1993 2016 2021 discussion 21-2
9. P.V. Finocchietto, M.C. Franco, S. Holod, A.S. Gonzalez, D.P. Converso, and V.G. Antico Arciuch Mitochondrial nitric oxide synthase: a masterpiece of metabolic adaptation, cell growth, transformation, and death Exp Biol Med (Maywood) 234 2009 1020 1028
10. N.A. Riobo, M. Melani, N. Sanjuan, M.L. Fiszman, M.C. Gravielle, and M.C. Carreras The modulation of mitochondrial nitric-oxide synthase activity in rat brain development J Biol Chem 277 2002 42447 42455
11. G.C. Brown Nitric oxide and neuronal death Nitric Oxide 23 2010 153 165
12. C. Iadecola, T. Kahles, E.F. Gallo, and J. Anrather Neurovascular protection by ischaemic tolerance: role of nitric oxide J Physiol 589 2011 4137 4145
13. A.L. Orr, S. Li, C.E. Wang, H. Li, J. Wang, and J. Rong N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking J Neurosci 28 2008 2783 2792
14. A.V. Panov, C.A. Gutekunst, B.R. Leavitt, M.R. Hayden, J.R. Burke, and W.J. Strittmatter Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines Nat Neurosci 5 2002 731 736
15. A. Lau, and M. Tymianski Glutamate receptors, neurotoxicity and neurodegeneration Pflugers Arch 460 2010 525 542
16. A. Novelli, J.A. Reilly, P.G. Lysko, and R.C. Henneberry Glutamate becomes neurotoxic via the N-methyl-d-aspartate receptor when intracellular energy levels are reduced Brain Res 451 1988 205 212
17. R. Sattler, Z. Xiong, W.Y. Lu, M. Hafner, J.F. MacDonald, and M. Tymianski Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein Science 284 1999 1845 1848
18. Y. Liu, T.P. Wong, M. Aarts, A. Rooyakkers, L. Liu, and T.W. Lai NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo J Neurosci 27 2007 2846 2857
19. F. Ichas, and J.P. Mazat From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state Biochim Biophys Acta 1366 1998 33 50
20. A. Schousboe, and H.S. Waagepetersen Role of astrocytes in glutamate homeostasis: implications for excitotoxicity Neurotox Res 8 2005 221 225
21. P. Lipton Ischemic cell death in brain neurons Physiol Rev 79 1999 1431 1568
22. G.B. Landwehrmeyer, D.G. Standaert, C.M. Testa, J.B. Penney Jr., and A.B. Young NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum J Neurosci 15 1995 5297 5307
23. A.J. Milnerwood, C.M. Gladding, M.A. Pouladi, A.M. Kaufman, R.M. Hines, and J.D. Boyd Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice Neuron 65 2010 178 190
24. Y. Sun, A. Savanenin, P.H. Reddy, and Y.F. Liu Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-d-aspartate receptors via post-synaptic density 95 J Biol Chem 276 2001 24713 24718
25. N. Chen, T. Luo, C. Wellington, M. Metzler, K. McCutcheon, and M.R. Hayden Subtype-specific enhancement of NMDA receptor currents by mutant huntingtin J Neurochem 72 1999 1890 1898
26. C. Song, Y. Zhang, C.G. Parsons, and Y.F. Liu Expression of polyglutamine-expanded huntingtin induces tyrosine phosphorylation of N-methyl-d-aspartate receptors J Biol Chem 278 2003 33364 33369
27. T.S. Tang, H. Tu, E.Y. Chan, A. Maximov, Z. Wang, and C.L. Wellington Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1 Neuron 39 2003 227 239
28. J.H. Cha, C.M. Kosinski, J.A. Kerner, S.A. Alsdorf, L. Mangiarini, and S.W. Davies Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene Proc Natl Acad Sci U S A 95 1998 6480 6485
29. B. Hassel, S. Tessler, R.L. Faull, and P.C. Emson Glutamate uptake is reduced in prefrontal cortex in Huntington's disease Neurochem Res 33 2008 232 237
30. C. Iadecola, and J. Anrather The immunology of stroke: from mechanisms to translation Nat Med 17 2011 796 808
31. J.P. Konsman, B. Drukarch, and A.M. Van Dam (Peri)vascular production and action of pro-inflammatory cytokines in brain pathology Clin Sci (Lond) 112 2007 1 25
32. J.M. Pocock, and H. Kettenmann Neurotransmitter receptors on microglia Trends Neurosci 30 2007 527 535
33. C. Iadecola, F. Zhang, S. Xu, R. Casey, and M.E. Ross Inducible nitric oxide synthase gene expression in brain following cerebral ischemia J Cereb Blood Flow Metab 15 1995 378 384
34. C. Iadecola, F. Zhang, and X. Xu Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage Am J Physiol 268 1995 R286 R292
35. N.M. Bornstein, B. Aronovich, A.D. Korczyn, S. Shavit, D.M. Michaelson, and J. Chapman Antibodies to brain antigens following stroke Neurology 56 2001 529 530
36. T. Moller Neuroinflammation in Huntington's disease J Neural Transm 117 2010 1001 1008
37. E. Sapp, K.B. Kegel, N. Aronin, T. Hashikawa, Y. Uchiyama, and K. Tohyama Early and progressive accumulation of reactive microglia in the Huntington disease brain J Neuropathol Exp Neurol 60 2001 161 172
38. A. Silvestroni, R.L. Faull, A.D. Strand, and T. Moller Distinct neuroinflammatory profile in post-mortem human Huntington's disease Neuroreport 20 2009 1098 1103
39. R. Brouns, R. Verkerk, T. Aerts, D. De Surgeloose, A. Wauters, and S. Scharpe The role of tryptophan catabolism along the kynurenine pathway in acute ischemic stroke Neurochem Res 35 2010 1315 1322
40. C.M. Forrest, G.M. Mackay, N. Stoy, S.L. Spiden, R. Taylor, and T.W. Stone Blood levels of kynurenines, interleukin-23 and soluble human leucocyte antigen-G at different stages of Huntington's disease J Neurochem 112 2010 112 122
41. M.N. Perkins, and T.W. Stone An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid Brain Res 247 1982 184 187
42. M. Kessler, T. Terramani, G. Lynch, and M. Baudry A glycine site associated with N-methyl-d-aspartic acid receptors: characterization and identification of a new class of antagonists J Neurochem 52 1989 1319 1328
43. C. Hilmas, E.F. Pereira, M. Alkondon, A. Rassoulpour, R. Schwarcz, and E.X. Albuquerque The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications J Neurosci 21 2001 7463 7473
44. M. Marchi, F. Risso, C. Viola, P. Cavazzani, and M. Raiteri Direct evidence that release-stimulating alpha7* nicotinic cholinergic receptors are localized on human and rat brain glutamatergic axon terminals J Neurochem 80 2002 1071 1078
45. S. Okuda, N. Nishiyama, H. Saito, and H. Katsuki 3-Hydroxykynurenine, an endogenous oxidative stress generator, causes neuronal cell death with apoptotic features and region selectivity J Neurochem 70 1998 299 307
46. L.P. de Carvalho, P. Bochet, and J. Rossier The endogenous agonist quinolinic acid and the non endogenous homoquinolinic acid discriminate between NMDAR2 receptor subunits Neurochem Int 28 1996 445 452
47. T.W. Stone, and M.N. Perkins Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS Eur J Pharmacol 72 1981 411 412
48. J.H. Connick, and T.W. Stone Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo Br J Pharmacol 93 1988 868 876
49. R.G. Tavares, C.I. Tasca, C.E. Santos, L.B. Alves, L.O. Porciuncula, and T. Emanuelli Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes Neurochem Int 40 2002 621 627
50. C. Rios, and A. Santamaria Quinolinic acid is a potent lipid peroxidant in rat brain homogenates Neurochem Res 16 1991 1139 1143
51. W.M. Behan, M. McDonald, L.G. Darlington, and T.W. Stone Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl Br J Pharmacol 128 1999 1754 1760
52. T.W. Stone, C.M. Forrest, N. Stoy, and L.G. Darlington Involvement of kynurenines in Huntington's disease and stroke-induced brain damage J Neural Transm. 119 2012 261 274
53. K. Nozaki, and M.F. Beal Neuroprotective effects of L-kynurenine on hypoxia-ischemia and NMDA lesions in neonatal rats J Cereb Blood Flow Metab 12 1992 400 407
54. K. Sas, K. Csete, L. Vecsei, and J.G. Papp Effect of systemic administration of L-kynurenine on corticocerebral blood flow under normal and ischemic conditions of the brain in conscious rabbits J Cardiovasc Pharmacol 42 2003 403 409
55. G. Gigler, G. Szenasi, A. Simo, G. Levay, L.G. Harsing Jr., and K. Sas Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils Eur J Pharmacol 564 2007 116 122
56. K. Sas, H. Robotka, E. Rozsa, M. Agoston, G. Szenasi, and G. Gigler Kynurenine diminishes the ischemia-induced histological and electrophysiological deficits in the rat hippocampus Neurobiol Dis 32 2008 302 308
57. H. Robotka, K. Sas, M. Agoston, E. Rozsa, G. Szenasi, and G. Gigler Neuroprotection achieved in the ischaemic rat cortex with L-kynurenine sulphate Life Sci 82 2008 915 919
58. J.M. Miller, U. MacGarvey, and M.F. Beal The effect of peripheral loading with kynurenine and probenecid on extracellular striatal kynurenic acid concentrations Neurosci Lett 146 1992 115 118
59. 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
60. C.A. Harris, A.F. Miranda, J.J. Tanguay, R.J. Boegman, R.J. Beninger, and K. Jhamandas Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain kynurenic acid Br J Pharmacol 124 1998 391 399
61. F. Moroni, A. Cozzi, F. Peruginelli, R. Carpenedo, and D.E. Pellegrini-Giampietro Neuroprotective effects of kynurenine-3-hydroxylase inhibitors in models of brain ischemia Adv Exp Med Biol 467 1999 199 206
62. F. Moroni, R. Carpenedo, A. Cozzi, E. Meli, A. Chiarugi, and D.E. Pellegrini-Giampietro Studies on the neuroprotective action of kynurenine mono-oxygenase inhibitors in post-ischemic brain damage Adv Exp Med Biol 527 2003 127 136
63. A. Cozzi, R. Carpenedo, and F. Moroni Kynurenine hydroxylase inhibitors reduce ischemic brain damage: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[- N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61-8048) in models of focal or global brain ischemia J Cereb Blood Flow Metab 19 1999 771 777
64. 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
65. 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
66. T.W. Stone Development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection Trends Pharmacol Sci 21 2000 149 154
67. R. Schwarcz The kynurenine pathway of tryptophan degradation as a drug target Curr Opin Pharmacol 4 2004 12 17
68. F. Fulop, I. Szatmari, E. Vamos, D. Zadori, J. Toldi, and L. Vecsei Syntheses, transformations and pharmaceutical applications of kynurenic acid derivatives Curr Med Chem 16 2009 4828 4842
69. P. Guidetti, H.Q. Wu, and R. Schwarcz In situ produced 7-chlorokynurenate provides protection against quinolinate- and malonate-induced neurotoxicity in the rat striatum Exp Neurol 163 2000 123 130
70. C.J. Parli, P. Krieter, and B. Schmidt Metabolism of 6-chlorotryptophan to 4-chloro-3-hydroxyanthranilic acid: a potent inhibitor of 3-hydroxyanthranilic acid oxidase Arch Biochem Biophys 203 1980 161 166
71. L. Gellert, J. Fuzik, A. Goblos, K. Sarkozi, M. Marosi, and Z. Kis Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia Eur J Pharmacol 667 2011 182 187
72. D. Zadori, G. Nyiri, A. Szonyi, I. Szatmari, F. Fulop, 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