喹啉酸
犬尿氨酸
犬尿氨酸途径
巴比妥酸
神经保护
吲哚胺2,3-双加氧酶
多发性硬化
神经毒性
免疫系统
药理学
炎症
烟酰胺腺嘌呤二核苷酸
化学
生物
医学
生物化学
氨基酸
色氨酸
免疫学
酶
NAD+激酶
内科学
毒性
作者
Ananda Staats Pires,Gayathri Sundaram,Benjamin Heng,Shivani Krishnamurthy,Bruce J. Brew,Gilles J. Guillemin
标识
DOI:10.1016/j.pharmthera.2021.108055
摘要
The kynurenine pathway (KP) is the major catabolic pathway for the essential amino acid tryptophan leading to he production of nicotinamide adenine dinucleotide. In inflammatory conditions, the activation of the KP leads to the production of several bioactive metabolites including kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, kynurenic acid and quinolinic acid. These metabolites can have redox and immune suppressive activity, be neurotoxic or neuroprotective. While the activity of the pathway is tightly regulated under normal physiological condition, it can be upregulated by immunological activation and inflammation. The dysregulation of the KP has been implicated in wide range of neurological diseases and psychiatric disorders. In this review, we discuss the mechanisms involved in KP-mediated neurotoxicity and immune suppression, and its role in diseases of our expertise including cancer, chronic pain and multiple sclerosis. We also provide updates on the clinical trials evaluating the efficacy of KP inhibitors and/or analogues in each respective disease.
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