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The Role of the Kynurenine Pathway in Neurodegenerative Diseases

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Book cover Targeting the Broadly Pathogenic Kynurenine Pathway

Abstract

The kynurenine pathway, the main metabolic route of tryptophan degradation, produces several neuroactive molecules. Alterations in the kynurenine pathway have been described in a number of neurological disorders; a feature of special importance is the elevation of neurotoxic metabolites, which may promote glutamate-mediated excitotoxic neuronal damage. The delicate balance between the neurotoxic and neuroprotective compounds participating in the kynurenine pathway has been suggested to play an important role in the regulation of glutamatergic neurotransmission and in inflammatory processes. Synthetic kynurenic acid derivatives and kynurenine-monooxygenase inhibitors have proved in several preclinical studies to have beneficial effects. The kynurenine pathway offers a promising target for future drug development with the aim of achieving neuroprotection.

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Abbreviations

3-HANA:

3-Hydroxyanthranilic acid

3-OH-KYN:

3-Hydroxykynurenine

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

AMPA:

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

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

EAE:

Experimental autoimmune encephalomyelitis

Glu:

Glutamate

HD:

Huntington’s disease

IDO:

Indoleamine-2,3-dioxygenase

KAT:

Kynurenine aminotransferase

KMO:

Kynurenine monooxygenase

KP:

Kynurenine pathway

KYN:

Kynurenine

KYNA:

Kynurenic acid

MPTP:

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

MS:

Multiple sclerosis

NMDA:

N-methyl-d-aspartate

PD:

Parkinson’s disease

QUIN:

Quinolinic acid

TDO:

Tryptophan-2,3-dioxygenase

Trp:

Tryptophan

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Acknowledgements

This work was supported by the project TÁMOP-4.2.2.A-11/1/KONV-2012-0052, the Hungarian Brain Research Program (NAP, Grant No. KTIA_13_NAP-A-III/9.), and the MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences and the University of Szeged. Thanks are due to David Durham from the UK for the linguistic corrections of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary

    Zsófia Majláth & László Vécsei

  2. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary

    József Toldi

  3. MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary

    József Toldi & László Vécsei

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  1. Zsófia Majláth
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  2. József Toldi
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Correspondence to László Vécsei .

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

    Sandeep Mittal

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Majláth, Z., Toldi, J., Vécsei, L. (2015). The Role of the Kynurenine Pathway in Neurodegenerative Diseases. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_15

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