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Neuropathology of Kynurenine Pathway of Tryptophan Metabolism

  • Neuropharmacology (R Pi and G Aston-Jones, Section Editors)
  • Published:
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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.

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Abbreviations

KP:

Kynurenine pathway

KYN:

Kynurenine

KYNA:

Kynurenic acid

TRP:

Tryptophan

3-HK:

3-Hydroxykynurenine

AA:

Anthranilic acid

XA:

Xanthurenic acid

TDO:

Tryptophan 2, 3 dioxygenase

IDO:

Indoleamine 2, 3 dioxygenase

KAT:

Kynurenine aminotransferase

KMO:

Kynurenine monoxygenase

NAD:

Nicotinamide adenine dinucleotide

BDL:

Bile duct ligation

NMDA:

N-methyl D-aspartate

GSH:

Glutathione

TPH:

Tryptophan hydroxylase

5-HIAA:

5-hydroxyindoleacetic acid

BD:

Bipolar disorders

HD:

Huntington disease

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

MDD:

Major depressive disorders

TLR:

Toll-like receptors

MT:

1-Methyl tryptophan

BDNF:

Brain-derived neurotrophic factor

TrkB:

Tropomycin receptor kinase B

PFC:

Prefrontal cortex

CA3:

Cornu ammonis of hippocampus

MS:

Multiple sclerosis

FNDC5:

Fibronectin type III domain containing 5

CSF:

Cerebrospinal fluid

PPI:

Prepulse Inhibition

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PIC:

Picolinic acid

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  1. CESP/National Institute of Health and Medical Research INSERM UMR-S 1178, Paris-Sud University, Faculty of Pharmacy, Paris-Saclay University, Orsay, France

    Abdulkarim Tutakhail, Sarah Khabil & François Coudoré

  2. Pharmacology Department, Faculty of Pharmacy, Kabul University, Kabul, Afghanistan

    Abdulkarim Tutakhail, Qand Agha Nazari & Hafiza Hamid

  3. Biochemistry Department, Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France

    Lysiane Boulet

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Tutakhail, A., Boulet, L., Khabil, S. et al. Neuropathology of Kynurenine Pathway of Tryptophan Metabolism. Curr Pharmacol Rep 6, 8–23 (2020). https://doi.org/10.1007/s40495-019-00208-2

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