Review3-Hydroxykynurenine: An intriguing molecule exerting dual actions in the Central Nervous System

Kynurenine pathway is gaining attention due to the many metabolic processes in which it has been involved. The tryptophan conversion into several other metabolites through this pathway provides neuronal and redox modulators useful for maintenance of major functions in the brain. However, when physiopathological conditions prevail - i.e. oxidative stress, excitotoxicity, and inflammation - preferential formation and accumulation of toxic metabolites could trigger factors for degeneration in neurological disorders. 3-Hydroxykynurenine has been largely described as one of these toxic metabolites capable of inducing oxidative damage and cell death; consequently, this metabolite has been hypothesized to play a pivotal role in different neurological and psychiatric disorders. Supporting evidence has shown altered 3-hydroxykynurenine levels in samples of patients from several disorders. In contrast, some experimental studies have provided evidence of antioxidant and scavenging properties inherent to this molecule. In this review, we explored most of literature favoring one or the other concept, in order to provide an accurate vision on the real participation of this tryptophan metabolite in both experimental paradigms and human brain pathologies. Through this collected evidence, we provide an integrative hypothesis on how 3-hydroxykynurenine is exerting its dual actions in the Central Nervous System and what will be the course of investigations in this field for the next years.

► Kynurenine pathway is involved in physiological and physiopathological events. ► 3-hydroxykynurenine is a metabolite exhibiting dual actions in the brain. ► Antioxidant and scavenging properties have been described for this metabolite. ► Oxidative stress and cell damage are also produced by 3-hydroxykynurenine. ► An integrative hypothesis on these effects is proposed.