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The Role of Kynurenine Pathway Metabolites in Neuropsychiatric Disorders

  • Chapter
Targeting the Broadly Pathogenic Kynurenine Pathway

Abstract

In recent years, the role of kynurenine and its neuroactive metabolites as they relate to human disease has been intensely studied. Though much work has focused on kynurenine metabolism in neurodegenerative diseases, it is becoming clear that disruption of this pathway can have profound behavioral effects that are also relevant for neuropsychiatric indications. The following chapter will review both preclinical and clinical studies where kynurenine and its most abundant metabolic products were evaluated in relation to a range of highly prevalent neuropsychiatric disorders including schizophrenia, depression, and ADHD. Each section will summarize the kynurenine disruptions thought to be associated with a particular disorder, discuss the functional consequences of these effects, and speculate on means to improve unmet medical needs through manipulation of the kynurenine pathway.

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Abbreviations

1-MT:

1-Methyl tryptophan

3-HANA:

3-Hydroxyanthranilic acid

α7nAChR:

α7 Nicotinic acetylcholine receptors

AA:

Anthranillic acid

BCG:

Bacillus Calmette-Guerin

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

FST:

Forced swim test

IDO:

Indoleamine 2,3-dioxygenase

3-HK:

3-Hydroxykynurenine

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

KATs:

Kynurenine aminotransferases

KMO:

Kynurenine monooxygenase

KOKP:

Kynurenine pathway Knockout

KYN:

l-Kynurenine

KYNA:

Kynurenic acid

LPS:

Magnesium

MDD:

Major depressive disorde

NMDA:

N-methyl-d-aspartate

QUIN:

Quinolinic acid

SNP:

Single-nucleotide polymorphism

TDO:

Tryptophan 2,3-dioxygenase

TTrp:

tryptophan

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Authors and Affiliations

  1. Lundbeck Research USA, 215 College Rd, Paramus, NJ, 07652, USA

    Brian M. Campbell

  2. Maryland Psychiatric Research Center, University of Maryland School of Medicine, 55 Wade Ave, Baltimore, MD, 21228, USA

    Ana Pocivavsek & Francesca M. Notarangelo

  3. Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark

    Anna I. Parachikova

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  1. Brian M. Campbell
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  2. Ana Pocivavsek
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  4. Anna I. Parachikova
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Correspondence to Brian M. Campbell .

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  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Campbell, B.M., Pocivavsek, A., Notarangelo, F.M., Parachikova, A.I. (2015). The Role of Kynurenine Pathway Metabolites in Neuropsychiatric Disorders. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_19

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