犬尿氨酸3-单加氧酶在疾病中的作用及其靶向药物研究进展
Advances in the role of kynurenine 3-monooxygenase in disease and its target drugs
王燚 1魏伟 1常艳1
作者信息
- 1. 安徽医科大学临床药理研究所/抗炎免疫药物教育部重点实验室/安徽省抗炎免疫药物协同创新中心/安徽医科大学类风湿关节炎研究中心,安徽合肥 230000
- 折叠
摘要
犬尿氨酸3-单加氧酶(kynurenine 3-monooxygenase,KMO)是机体犬尿氨酸代谢途径(kynurenine pathway,KP)分解代谢下游的一种关键限速酶.在KMO催化下,中间产物犬尿氨酸被代谢为多种活性代谢物,包括3-羟基犬尿氨酸(3-hydroxykynurenine,3-HK)、喹啉酸(quinolinic acid,QA)和烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD+)等.越来越多的研究表明,KMO表达活性异常介导KP代谢紊乱,参与了神经系统疾病、自身免疫病、感染性疾病及肿瘤等的发生发展,提示其可作为一个潜在、有效的药物治疗靶点.本文重点介绍KMO在多种疾病病理机制中的作用,并总结了已有的KMO抑制剂,为靶向KMO治疗提供方法和思路.
Abstract
Kynurenine 3-monooxygenase(KMO)is a key rate-limiting enzyme in the downstream catabolism of kynurenine pathway(KP).Under the catalysis of KMO,the intermediate product kynurenine is metabolized into various active metabolites,including 3-hydroxykynurenine(3-HK),quinolinic acid(QA)and nicotinamide adenine dinucleotide(NAD+).More and more studies have shown that abnormal KMO expression activity mediates KP metabolic disorders,and is involved in the occurrence and development of nervous system diseases,autoimmune diseases,infectious diseases and tumors,suggesting that KMO can be used as a potential and effective drug therapeutic target.This article focuses on the role of KMO in the pathological mechanism of various diseases,and summarizes the existing KMO inhibitors to provide methods and ideas for targeted KMO therapy.
关键词
犬尿氨酸3-单加氧酶/犬尿氨酸途径/肿瘤/神经系统/免疫系统Key words
kynurenine 3-monooxygenase/kynurenine pathway/tumour/nervous system/immune system引用本文复制引用
基金项目
安徽省自然科学基金面上项目(2108085MH320)
省留学人员创新项目择优资助计划(200LCX019)
出版年
2024
NETL
NSTL
万方数据