Neuropathology of Kynurenine Pathway of Tryptophan Metabolism

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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.

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Fig. 1



Kynurenine pathway




Kynurenic acid






Anthranilic acid


Xanthurenic acid


Tryptophan 2, 3 dioxygenase


Indoleamine 2, 3 dioxygenase


Kynurenine aminotransferase


Kynurenine monoxygenase


Nicotinamide adenine dinucleotide


Bile duct ligation


N-methyl D-aspartate




Tryptophan hydroxylase


5-hydroxyindoleacetic acid


Bipolar disorders


Huntington disease


Alzheimer’s disease


Parkinson’s disease


Major depressive disorders


Toll-like receptors


1-Methyl tryptophan


Brain-derived neurotrophic factor


Tropomycin receptor kinase B


Prefrontal cortex


Cornu ammonis of hippocampus


Multiple sclerosis


Fibronectin type III domain containing 5


Cerebrospinal fluid


Prepulse Inhibition




Picolinic acid


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Tutakhail, A., Boulet, L., Khabil, S. et al. Neuropathology of Kynurenine Pathway of Tryptophan Metabolism. Curr Pharmacol Rep (2020) doi:10.1007/s40495-019-00208-2

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  • Kynurenine pathway
  • KYNs
  • Excitotoxicity
  • Neuropsychiatric diseases
  • Neurodegenerative diseases