Endogenous kynurenines as targets for drug discovery and development

被引:653
作者
Stone, TW
Darlington, LG
机构
[1] Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
[2] Epsom Gen Hosp, Epsom KT18 7EG, Surrey, England
关键词
D O I
10.1038/nrd870
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The kynurenine pathway is the main pathway for tryptophan metabolism. It generates compounds that can modulate activity at glutamate receptors and possibly nicotinic receptors, in addition to some as-yet-unidentified sites. The pathway is in a unique position to regulate other aspects of the metabolism of tryptophan to neuroactive compounds, and also seems to be a key factor in the communication between the nervous and immune systems. It also has potentially important roles in the regulation of cell proliferation and tissue function in the periphery. As a result, the pathway presents a multitude of potential sites for drug discovery in neuroscience, oncology and visceral pathology.
引用
收藏
页码:609 / 620
页数:12
相关论文
共 145 条
[1]   Elucidation of a novel polypeptide cross-link involving 3-hydroxykynurenine [J].
Aquilina, JA ;
Carver, JA ;
Truscott, RJW .
BIOCHEMISTRY, 1999, 38 (35) :11455-11464
[2]   Increased kynurenic acid levels and decreased brain kynurenine aminotransferase I in patients with down syndrome [J].
Baran, H ;
Cairns, N ;
Lubec, B ;
Lubec, G .
LIFE SCIENCES, 1996, 58 (21) :1891-1899
[3]   Kynurenic acid influences the respiratory parameters of rat heart mitochondria [J].
Baran, H ;
Staniek, K ;
Kepplinger, B ;
Gille, L ;
Stolze, K ;
Nohl, H .
PHARMACOLOGY, 2001, 62 (02) :119-123
[4]   Increased kynurenic acid in the brain after neonatal asphyxia [J].
Baran, H ;
Kepplinger, B ;
Herrera-Marschitz, M ;
Stolze, K ;
Lubec, G ;
Nohl, H .
LIFE SCIENCES, 2001, 69 (11) :1249-1256
[5]   Temporal and spatial changes of quinolinic acid immunoreactivity in the gerbil hippocampus following transient cerebral ischemia [J].
Barattè, S ;
Molinari, A ;
Veneroni, O ;
Speciale, C ;
Benatti, L ;
Salvati, P .
MOLECULAR BRAIN RESEARCH, 1998, 59 (01) :50-57
[6]  
BARON BM, 1992, J PHARMACOL EXP THER, V262, P947
[7]  
BEAL MF, 1991, J NEUROSCI, V11, P1649
[8]  
BEAL MF, 1992, J NEUROL SCI, V108, P80
[9]   REPLICATION OF THE NEUROCHEMICAL CHARACTERISTICS OF HUNTINGTONS-DISEASE BY QUINOLINIC ACID [J].
BEAL, MF ;
KOWALL, NW ;
ELLISON, DW ;
MAZUREK, MF ;
SWARTZ, KJ ;
MARTIN, JB .
NATURE, 1986, 321 (6066) :168-171
[10]   Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl [J].
Behan, WMH ;
McDonald, M ;
Darlington, LG ;
Stone, TW .
BRITISH JOURNAL OF PHARMACOLOGY, 1999, 128 (08) :1754-1760