The tryptophan metabolism, kynurenine pathway and oxidative stress - implications for glioma pathobiology

Abstract

The kynurenine pathway receives increasing attention due to its involvement in central nervous system pathologies, i.a. neurodegenerative and psychiatric disorders, but also due to the contribution to the pathomechanism of neoplasms, including brain tumors. The present review focuses on kynurenine pathway activity in gliomas, brain tumors of glial origin. The upregulation of kynurenine pathway enzyme, indoleamine 2,3-dioxygenase (IDO), resulting in a decreased level of tryptophan and augmented kynurenine synthesis (increased (KYN/Trp ratio) are the most recognised hallmark of malignant transformation, characterised with immunomodulatory adaptations, providing an escape from defence mechanisms of the host, growth-beneficial milieu and resistance to some therapeutics. The review addresses, however, the oxidative/nitrosative stress-associated mechanisms of tryptophan catabolism, mainly the kynurenine pathway activity, linking them with glioma pathobiology.

Keywords: Glioma; IDO; Kynurenine pathway; Oxidative stress; Tryptophan.