title: Tryptophan, adenosine, neurodegeneration and neuroprotection.
abstract: This review summarises the potential contributions of two groups of compounds to cerebral dysfunction and damage in metabolic disease. The kynurenines are oxidised metabolites of tryptophan, the kynurenine pathway being the major route for tryptophan catabolism in most tissues. The pathway includes quinolinic acid -- an agonist at N-methyl-D-aspartate (NMDA) receptors, kynurenic acid -- an antagonist at glutamate and nicotinic receptors, and other redox active compounds that are able to generate free radicals under many physiological and pathological conditions. The pathway is activated in immune-competent cells, including glia in the central nervous system, and may contribute substantially to delayed neuronal damage following an infarct or metabolic insult. Adenosine is an ubiquitous purine that can protect neurons by suppressing excitatory neurotransmitter release, reducing calcium fluxes and inhibiting NMDA receptors. The extent of brain injury is critically dependent on the balance between the two opposing forces of kynurenines and purines.
authors: Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, Scotland, UK. t.w.stone@bio.gla.ac.uk
authors: T W
authors: TW
authors: Stone
authors: C M
authors: CM
authors: Forrest
authors: G M
authors: GM
authors: Mackay
authors: N
authors: N
authors: Stoy
authors: L G
authors: LG
authors: Darlington
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007737:Kynurenine / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology*; D018696:Neuroprotective Agents; D018384:Oxidative Stress; D017378:Quinolinic Acid / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018047:Receptors, Purinergic P1 / Q000502:physiology; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D009243:NAD; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid; D000241:Adenosine
references: Neuroreport. 1997 Jan 20;8(2):431-4
references: 9080423
references: Carcinogenesis. 1995 Feb;16(2):349-56
references: 7859368
references: Br J Pharmacol. 1999 Jun;127(3):729-39
references: 10401564
references: Brain Res. 1995 Dec 24;705(1-2):79-84
references: 8821736
references: Life Sci. 1979 May 28;24(22):2083-92
references: 459704
references: Neuroscience. 1998 Jul;85(1):229-37
references: 9607714
references: J Leukoc Biol. 1995 Feb;57(2):199-206
references: 7852833
references: Proc Natl Acad Sci U S A. 1988 Jun;85(11):4079-81
references: 2967497
references: Brain Res. 1994 Apr 4;641(2):217-24
references: 8012824
references: Neurosci Lett. 1992 Sep 28;145(1):67-70
references: 1461571
references: Neurochem Res. 1991 Oct;16(10):1139-43
references: 1686636
references: J Neural Transm (Vienna). 1998;105(2-3):161-72
references: 9660094
references: J Neurosci Res. 1989 Feb;22(2):150-7
references: 2523487
references: Neuroscience. 1997 Feb;76(3):749-61
references: 9135048
references: Neurochem Res. 1990 Nov;15(11):1101-7
references: 2089269
references: Neurosci Lett. 1989 Jun 19;101(2):191-6
references: 2771165
references: Neurochem Res. 1998 May;23(5):661-5
references: 9566604
references: Br J Pharmacol. 1990 Aug;100(4):814-8
references: 2207501
references: Br J Pharmacol. 1993 Jun;109 (2):316-21
references: 8358536
references: Jpn J Pharmacol. 1996 Jun;71(2):183-6
references: 8835646
references: Circ Res. 1979 Oct;45(4):486-92
references: 476871
references: Nat Rev Drug Discov. 2002 Aug;1(8):609-20
references: 12402501
references: J Neural Transm Gen Sect. 1995;102(1):67-73
references: 8785025
references: Neuroscience. 1987 Nov;23 (2):423-32
references: 2963969
references: Eur J Pharmacol. 1988 Sep 1;154(1):85-7
references: 2846328
references: J Neurochem. 2004 Jun;89(5):1101-10
references: 15147502
references: Neuropharmacology. 2005 Mar;48(4):517-24
references: 15755479
references: Brain Res Mol Brain Res. 1998 Aug 15;59(1):50-7
references: 9729272
references: Neurochem Res. 2005 Oct;30(10):1311-8
references: 16341593
references: J Cereb Blood Flow Metab. 1990 Sep;10(5):660-7
references: 1696582
references: Brain Res. 1982 Sep 9;247(1):184-7
references: 6215086
references: J Neurotrauma. 1997 Feb;14(2):89-98
references: 9069440
references: AJNR Am J Neuroradiol. 2005 Feb;26(2):347-51
references: 15709133
references: Neuropsychopharmacology. 1996 Oct;15(4):382-9
references: 8887992
references: Science. 1990 Dec 14;250(4987):1593-6
references: 2148832
references: J Neurovirol. 1995 Dec;1(5-6):375-80
references: 9222380
references: Brain Res. 1993 Dec 31;632(1-2):314-6
references: 8149236
references: Cerebrovasc Brain Metab Rev. 1992 Winter;4(4):346-69
references: 1486019
references: Brain. 1992 Oct;115 ( Pt 5):1249-73
references: 1422788
references: Brain Res. 1990 Apr 2;512(2):269-76
references: 1972342
references: J Neurovirol. 1996 Dec;2(6):433-8
references: 8972426
references: Prog Neurobiol. 2001 Jun;64(2):185-218
references: 11240212
references: Neurochem Int. 2005 Jul;47(1-2):31-8
references: 15908047
references: J Neurochem. 1986 Dec;47(6):1667-71
references: 2430055
references: Biochem J. 1996 Dec 1;320 ( Pt 2):595-7
references: 8973572
references: Br J Pharmacol. 1993 Sep;110(1):470-6
references: 8220909
references: Pediatr Neurol. 1994 Feb;10(1):9-12
references: 8198681
references: J Cereb Blood Flow Metab. 1998 Jun;18(6):610-5
references: 9626184
references: Brain. 1995 Jun;118 ( Pt 3):735-52
references: 7600090
references: J Neurochem. 1998 Jan;70(1):299-307
references: 9422375
references: Neurochem Int. 2004 Jan;44(2):83-90
references: 12971910
references: Science. 1983 Jan 21;219(4582):316-8
references: 6849138
references: Pediatr Res. 1992 Oct;32(4):483-8
references: 1279510
references: Exp Neurol. 1997 Apr;144(2):287-301
references: 9168830
references: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2769-73
references: 8464887
references: Brain Res. 1989 Aug 28;495(2):225-31
references: 2765927
references: Biochem Pharmacol. 1989 May 15;38(10 ):1555-62
references: 2525040
references: Brain Res. 1998 Mar 23;787(2):348-50
references: 9518688
references: Crit Care Med. 1999 Mar;27(3):493-7
references: 10199527
references: Br J Pharmacol. 1999 Dec;128(8):1754-60
references: 10588931
references: J Chem Neuroanat. 1998 Jun;14(3-4):151-6
references: 9704893
references: Metab Brain Dis. 2005 Dec;20(4):253-63
references: 16382336
references: Brain Res. 1998 Aug 3;800(2):328-35
references: 9685693
references: Br J Pharmacol. 1997 Sep;122(1):71-80
references: 9298530
references: J Neurochem. 1990 Jul;55(1):338-41
references: 2141357
references: Neuroreport. 1998 Dec 1;9(17):3955-9
references: 9875735
references: Ann N Y Acad Sci. 1997 Oct 15;825:30-48
references: 9369973
references: Am J Vet Res. 2002 Aug;63(8):1167-71
references: 12171172
references: Pharmacol Rev. 1993 Sep;45(3):309-79
references: 8248282
references: J Neurosci Res. 2004 Feb 1;75(3):436-40
references: 14743457
references: Eur J Pharmacol. 1995 Dec 20;287(3):295-302
references: 8991804
references: Eur J Pharmacol. 1981 Jul 10;72(4):411-2
references: 6268428
references: Neuroscience. 1989;30(2):451-62
references: 2747922
references: Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12553-8
references: 8901620
references: Eur J Pharmacol. 1999 Mar 26;369(3):313-7
references: 10225368
references: J Chromatogr. 1991 Apr 19;565(1-2):436-40
references: 1874889
references: Eur J Pharmacol. 1984 Jan 27;97(3-4):341-2
references: 6323196
references: Stroke. 1990 Dec;21(12):1727-33
references: 2264080
references: Br J Pharmacol. 1989 Sep;98(1):225-35
references: 2804547
references: Cell Tissue Res. 1997 Dec;290(3):633-9
references: 9369539
references: J Neurol Sci. 1993 Feb;114(2):119-22
references: 8445391
references: Neuroreport. 1995 May 30;6(8):1097-100
references: 7662885
references: Br J Pharmacol. 2002 Mar;135(6):1435-42
references: 11906956
references: Int J Biochem Cell Biol. 2003 Aug;35(8):1175-81
references: 12757755
references: Naunyn Schmiedebergs Arch Pharmacol. 1990 Mar;341(3):225-31
references: 2342603
references: Lancet. 1989 Oct 21;2(8669):979-80
references: 2571888
references: J Neurosci. 1999 Nov 1;19(21):9192-200
references: 10531422
references: Eur J Med Chem. 2000 Feb;35(2):179-86
references: 10758280
references: Biochem Pharmacol. 1987 Jan 15;36(2):211-7
references: 2949752
references: Life Sci. 1994;55(3):PL61-5
references: 8007757
references: Eur J Pharmacol. 1998 Nov 27;362(1):17-25
references: 9865525
references: Neurosci Lett. 1989 Feb 27;97(3):271-5
references: 2524015
references: Trends Pharmacol Sci. 2000 Apr;21(4):149-54
references: 10740291
references: Eur J Neurosci. 2004 Aug;20(3):719-28
references: 15255982
references: Eur J Pharmacol. 2001 Sep 7;427(1):13-25
references: 11553359
references: Neuroscience. 1992 Nov;51(1):25-39
references: 1465184
references: Neurochem Int. 2003 Sep-Oct;43(4-5):493-9
references: 12742096
references: Brain Res. 1994 Jan 7;633(1-2):348-52
references: 8137170
references: Cell Tissue Res. 1994 Dec;278(3):461-9
references: 7850857
references: Neurosci Lett. 1994 Sep 12;178(2):211-5
references: 7824198
references: J Neurochem. 1993 Feb;60(2):768-71
references: 8419552
references: Brain Res. 1990 Oct 22;530(2):330-4
references: 1702344
references: Neuron. 1992 Jun;8(6):1139-50
references: 1351733
references: Brain Res. 1993 Oct 1;623(2):337-40
references: 8221118
references: J Neurochem. 1995 Feb;64(2):932-5
references: 7830088
references: J Neurosci Res. 2002 Jun 1;68(5):622-6
references: 12111852
references: Brain Res. 1996 Jun 24;725(1):115-20
references: 8828594
references: J Interferon Cytokine Res. 1997 Oct;17(10):589-95
references: 9355959
references: Brain Res. 1989 Jul 10;491(2):212-26
references: 2504437
references: Neurochem Int. 2005 Jul;47(1-2):51-7
references: 15985217
references: Brain Res. 1989 Jul 3;491(1):173-9
references: 2475209
references: J Neurochem. 1986 Mar;46(3):869-74
references: 2419500
references: Neurosci Lett. 1992 Sep 14;144(1-2):199-201
references: 1436703
references: J Neurochem. 1987 Jul;49(1):227-31
references: 3585332
references: Brain Res Mol Brain Res. 1999 Jan 22;64(1):59-68
references: 9889320
references: AIDS. 1998 Mar 5;12(4):355-63
references: 9520164
references: Gastroenterology. 1995 Mar;108(3):818-23
references: 7875484
references: J Neurochem. 1995 Nov;65(5):2235-40
references: 7595512