Abstract
The metabolism of tryptophan mostly proceeds through the kynurenine pathway. The biochemical
reaction includes both an agonist (quinolinic acid) at the N-methyl-d-aspartate receptor and an antagonist (kynurenic acid). Besides the N-methyl-d-aspartate antagonism, an important feature of kynurenic acid is the blockade of the
alpha7-nicotinic acetylcholine receptor and its influence on the alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic
acid receptor.
Kynurenic acid has proven to be neuroprotective in several experimental settings.
On the other hand, quinolinic acid is a potent neurotoxin with an additional and marked
free radical-producing property.
In consequence of these various receptor activities, the possible roles of these substances
in various neurological disorders have been proposed. Moreover, the possibility of
influencing the kynurenine pathway to reduce quinolinic acid and increase the level
of kynurenic acid in the brain offers a new target for drug action designed to change
the balance, decreasing excitotoxins and enhancing neuroprotectants. This review surveys
both the early and the current research in this field, focusing on the possible therapeutic
effects of kynurenines.
Abbreviations:
3-HA (3-hydroxyanthranilic acid), 3-HK (3-hydroxykynurenine), AD (Alzheimer's disease), AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid), ANA (anthranilic acid), BBB (blood-brain barrier), CSD (cortical spreading depression), EAA (excitatory amino acid), HD (Huntington's disease), HIV (human immunodeficiency virus), IDO (indoleamine 2,3-dioxygenase), KAT (kynurenine aminotransferase), KP (kynurenine pathway), KYNA (kynurenic acid), L-KYN (L-Kynurenine), NAD (nicotine adenine dinucleotide), NADP (NAD phosphate), NMDA (N-methyl-d-aspartate), PD (Parkinson's disease), QUIN (quinolinic acid), TRP (tryptophan), α7-nACh (alpha7-nicotinic acetylcholine), α-MTRP (alpha-[11C]me-L-TRP)Keywords
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Published online: March 06, 2009
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© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
