Therapeutic potential of targeting kynurenine pathway in neurodegenerative diseases

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. [Display omitted] •KP contains several neuroactive metabolites such as KA and QA.•The dysregulation of KP is involved in aging and NDs.•Targeting KP enzymes is beneficial for the treatment of NDs.•This review shows recent advance in development of KP modulators for NDs treatment.