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Neuroprotection by Kynurenine Metabolites

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Handbook of Neurotoxicity

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Abstract

The overexcitation of excitatory amino acid receptors generates excitotoxicity, which plays an important role in the pathophysiology of various neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases, stroke, and epilepsy. The prevention of excitotoxic neuronal damage is therefore a major objective in neuroprotective strategies. The kynurenine pathway, the main route of the tryptophan metabolism, produces both neuroprotective and neurotoxic metabolites. Kynurenic acid is a broad-spectrum endogenous antagonist of ionotropic excitatory amino acid receptors, and hence it can prevent excitotoxic neuronal damage. The kynurenine metabolites are additionally involved in the regulation of glutamatergic and cholinergic neurotransmission. The pathogeneses of several neurodegenerative disorders have been shown to involve multiple imbalances in the kynurenine metabolism. Kynurenine pathway metabolites may provide important targets for future neuroprotective therapeutic strategies.

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Abbreviations

3-HANA:

3-hydroxyanthranilic acid

AMPA:

alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ANA:

anthranilic acid

3-HK:

3-hydroxykynurenine

EAA:

excitatory amino acid

IDO:

indoleamine 2,3-dioxygenase

KAT:

kynurenine aminotransferase

KMO:

kynurenine 3-monooxygenase

KYNA:

kynurenic acid

L-KYN:

L-kynurenine

NAD:

nicotinamide adenine dinucleotide

NMDA:

N-methyl-D-aspartate

QUIN:

quinolinic acid

TDO:

tryptophan 2,3-dioxygenase

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Acknowledgments

This work was supported by the project “TÁMOP-4.2.1/B-09/1/KONV-2010-0005–Creating the Center of Excellence at the University of Szeged,” by the Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged, and by ETT 026–04.

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Authors and Affiliations

  1. Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged, Hungary

    Zsófia Majláth, Levente Szalárdy, Dénes Zádori, Péter Klivényi & László Vécsei

  2. Institute of Pharmaceutical Chemistry and Research Group of Stereochemistry, Hungarian Academy of Sciences, University of Szeged, Eötvös u. 6, Szeged, Hungary

    Ferenc Fülöp

  3. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép, fasor 52, Szeged, Hungary

    József Toldi

  4. Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged, Semmelweis u. 6, Szeged, Hungary

    József Toldi & László Vécsei

Authors
  1. Zsófia Majláth
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  2. Levente Szalárdy
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  3. Dénes Zádori
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  4. Péter Klivényi
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  5. Ferenc Fülöp
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  6. József Toldi
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  7. László Vécsei
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Corresponding author

Correspondence to László Vécsei .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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Majláth, Z. et al. (2014). Neuroprotection by Kynurenine Metabolites. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_165

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