Therapeutic potential of targeting kynurenine pathway in neurodegenerative diseases
Hualiang Shen1, Xinde Xu2, Yalong Bai2
1Zhejiang Engineering Research Center of Fat-soluble Vitamin, Shaoxing University, Shaoxing, 312000, China; College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing, 312000, China.
Abstract:
Kynurenine pathway (KP), the primary pathway of L-tryptophan (Trp) metabolism in mammals, contains several neuroactive metabolites such as kynurenic acid (KA) and quinolinic acid (QA). Its imbalance involved in aging and neurodegenerative diseases (NDs) has attracted much interest in therapeutically targeting KP enzymes and KP metabolite-associated receptors, especially kynurenine monooxygenase (KMO). Currently, many agents have been discovered with significant improvement in animal models but only one aryl hydrocarbon receptor (AHR) agonist 30 (laquinimod) has entered clinical trials for treating Huntington's disease (HD). In this review, we describe neuroactive KP metabolites, discuss the dysregulation of KP in aging and NDs and summarize the development of KP regulators in preclinical and clinical studies, offering an outlook of targeting KP for NDs treatment in future.
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