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Current Pharmacology Reports

, Volume 6, Issue 1, pp 8–23 | Cite as

Neuropathology of Kynurenine Pathway of Tryptophan Metabolism

  • Abdulkarim Tutakhail
  • Lysiane Boulet
  • Sarah Khabil
  • Qand Agha Nazari
  • Hafiza Hamid
  • François CoudoréEmail author
Neuropharmacology (R Pi and G Aston-Jones, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Neuropharmacology
  2. Topical Collection on Neuropharmacology

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.

Keywords

Kynurenine pathway KYNs Excitotoxicity Neuropsychiatric diseases Neurodegenerative diseases 

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

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights Informed Consent

This article does not contain any studies involving human or animal subjects performed by any of the authors.

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Abdulkarim Tutakhail
    • 1
    • 2
  • Lysiane Boulet
    • 3
  • Sarah Khabil
    • 1
  • Qand Agha Nazari
    • 2
  • Hafiza Hamid
    • 2
  • François Coudoré
    • 1
    Email author
  1. 1.CESP/National Institute of Health and Medical Research INSERM UMR-S 1178Paris-Sud University, Faculty of Pharmacy, Paris-Saclay UniversityOrsayFrance
  2. 2.Pharmacology Department, Faculty of PharmacyKabul UniversityKabulAfghanistan
  3. 3.Biochemistry DepartmentCentre Hospitalier Universitaire Grenoble-AlpesGrenobleFrance

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