The kynurenine pathway in chronic diseases: a compensatory mechanism or a driving force?

The kynurenine (KYN) pathway (KP) of tryptophan (TRP) metabolism is dysregulated in inflammation-driven pathologies including oncological and brain diseases [e.g., multiple sclerosis (MS), depression] and thus is a promising therapeutic target. Both pathological and compensatory mechanisms underlie diseaseassociated KP activation. There is growing evidence for bioenergetic roles of certain KP metabolites such as kynurenic acid (KA), or quinolinic acid (QA) as an NAD+ precursor, which may explain its frequently observed 'pathological' overactivation. Disease- and tissue-specific aspects, negative feedback on inflammatory signals, and the balance of downstream metabolites are likely to be decisive factors in the interpretation of an imbalanced KP. Therapeutic strategies should consider the compensatory actions and bioenergetic roles of KP metabolites to successfully design future theragnostic approaches aimed at attenuating disease progression.

Automated summary

The dysregulation of the kynurenine pathway in tryptophan metabolism is associated with inflammation-driven pathologies, making it a potential therapeutic target for diseases such as cancer and brain disorders. It is important to consider both compensatory mechanisms and bioenergetic roles of KP metabolites in designing effective therapeutic approaches to attenuate disease progression.