期刊
NEUROPHARMACOLOGY
卷 112, 期 -, 页码 264-274出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.01.011
关键词
Kynurenine pathway; Indoleamine 2,3-dioxygenase; Kynurenine 3-monooxygenase; Kynurenine aminotransferase; Kynurenine; Kynurenic acid; Quinolinic acid
资金
- JSPS KAKENHI [00612631, 26460675, 15H03086, 23390149]
- Smoking Research Foundation [4-7-2015]
- Grants-in-Aid for Scientific Research [15H03086, 23390149] Funding Source: KAKEN
The kynurenine pathway (KP) is the major route for tryptophan (TRP) metabolism in most mammalian tissues. The KP metabolizes TRP into a number of neuroactive metabolites, such as kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN). Elevated metabolite concentrations in the central nervous system are associated with the pathophysiology of several inflammation-related neuropsychiatric diseases. During an inflammatory response, the initial KP metabolic step is primarily regulated by indoleamine 2,3-dioxygenase 1 (ID01), which produces KYN from TRP. Following this initial step, the KP has 2 distinct branches; one branch is regulated by kynurenine 3-monooxygenase (KMO) and is primarily responsible for the 3-HK and QUIN production, and the other branch is regulated by kynurenine aminotransferase (KAT), which produces KYNA, an N-methyl-haspartate receptor and alpha-7-nicotinic acetylcholine receptor antagonist. Unbalanced KP metabolism has been demonstrated in distinct neuropsychiatric diseases; thus, understanding the mechanisms that regulate KP enzyme expression and activity is important. These enzymes are expressed by specific cell types, and the induction of enzyme expression by inflammatory stimuli also shows cell type specificity. This review provides an overview and discusses the current understanding of the influence of KP enzyme expression and activity in different cell types on the pathophysiological mechanisms of specific neuropsychiatric diseases. Moreover, the potential use of KP enzyme inhibition as a therapeutic strategy for treating neurological diseases is briefly discussed. This article is part of the Special Issue entitled `The Kynurenine Pathway in Health and Disease'. (C) 2016 Elsevier Ltd. All rights reserved.
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