title: An expanding range of targets for kynurenine metabolites of tryptophan.
abstract: The kynurenine pathway of tryptophan metabolism accounts for most of the tryptophan that is not committed to protein synthesis and includes compounds active in the nervous and immune systems. Kynurenine acts on the aryl hydrocarbon receptor, affecting the metabolism of xenobiotics and promoting carcinogenesis. Quinolinic acid is an agonist at N-methyl-D-aspartate receptors (NMDARs), but is also pro-oxidant, has immunomodulatory actions, and promotes the formation of hyperphosphorylated tau proteins. Kynurenic acid blocks NMDARs and α7-homomeric nicotinic cholinoceptors and is also an agonist at the orphan G-protein-coupled receptor GPR35. 3-Hydroxykynurenine and 3-hydroxyanthranilic acid have pronounced redox activity and regulate T cell function. Cinnabarinic acid can activate metabotropic glutamate receptors. This review highlights the increasing range of molecular targets for components of the kynurenine pathway in both the nervous and immune systems in relation to their relevance to disease and drug development.
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. trevor.stone@glasgow.ac.uk
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Stone
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stoy
authors.forename: L Gail
authors.initials: LG
authors.lastname: Darlington
mesh_terms: D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D007736:Kynurenic Acid / Q000494:pharmacology*; D007737:Kynurenine / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods*; D010084:Oxidation-Reduction; D017378:Quinolinic Acid / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid; D007736:Kynurenic Acid