Neuropathology of Kynurenine Pathway of Tryptophan Metabolism

Abstract

The different branches of kynurenine pathways of tryptophan metabolism are the important mechanism to elucidate various neurological and immunological disorders. There is a substantial body of evidence indicating the involvement of kynurenine pathway (KP) in the pathophysiology of some neuropsychiatric and neurodegenerative perturbation. This pathway generates neuro-active compounds, those can interact with neurotransmitters receptors in the central nervous system (CNS). According to some recent studies, there are a strong relation between KP’s related enzymes such as indoleamine 2,3 dioxygenase (IDO) and tryptophan 2,3 dioxygenase (TDO) activation and neurological disease. In this review article, we focus on the level/ratios of different metabolites and precursors such as tryptophan (TRP), 5-hydroxytryptamine (5-HT), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) in order to find the link with the KP-induced neuropathologies. Kynurenine metabolism is hypothesized to be one of the key mechanisms that link inflammation and depression. Some factors such as exercise (through PGC-1α), inflammation, stress, and some medication have the remarkable effects on KP. We highlight the role of different causes such as inflammation and stress, Tryptophan-kynurenine pathway with the whole biochemical and organ-specific biochemistry, and the neuropathomechanism of related pathologies. Here, we discuss the relations, the changes, and the mutual effects of KP with major depressive disorders, bipolar disorders, schizophrenia, Parkinson’s, and Alzheimer’s disease.