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Endogenous Kynurenic Acid and Neurotoxicity

  • Ewa M. UrbańskaEmail author
  • Iwona Chmiel-Perzyńska
  • Adam Perzyński
  • Marek Derkacz
  • Björn Owe-Larsson
Reference work entry

Abstract

Tryptophan metabolism along kynurenine pathway yields a number of compounds affecting brain function. Among kynurenine derivatives, neuroprotective kynurenic acid (KYNA) and neurotoxic quinolinic acid and 3-hydroxykynurenine have stimulated the greatest scientific interest. KYNA, initially considered merely a side-product of tryptophan degradation, was discovered in 1982 to act as excitatory amino acid receptor antagonist. Since then, a number of novel KYNA targets emerged. KYNA was suggested to play a role as antagonist of α7 nicotinic receptors and ligand of G protein-coupled GPR35 and human aryl hydrocarbon (AHR) receptors. In here, research data is reviewed supporting the idea that produced by astrocytes KYNA serves as an endogenous neuroprotectant. Mechanisms controlling brain levels of KYNA are discussed in the context of neurodegenerative disorders, brain ischemia, and seizures. Available data concerning changes of brain KYNA in respective animal models and in human diseases, together with an overview of effects following the application of KYNA, KYNA analogues or compounds influencing the activity of enzymes along kynurenine pathway are presented. Emerging therapies designed to increase the level of neuroprotective KYNA may become an important avenue in the treatment of brain disorders accompanied by neuronal loss.

Keywords

Ketogenic Diet Quinolinic Acid Kynurenine Pathway Cortical Slice Organotypic Hippocampal Slice Culture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ewa M. Urbańska
    • 1
    • 2
    Email author
  • Iwona Chmiel-Perzyńska
    • 1
  • Adam Perzyński
    • 3
  • Marek Derkacz
    • 4
  • Björn Owe-Larsson
    • 5
  1. 1.Laboratory of Cellular and Molecular Pharmacology, Department of Experimental and Clinical PharmacologyMedical University of LublinLublinPoland
  2. 2.Department of ToxicologyInstitute of Agricultural MedicineLublinPoland
  3. 3.Department of PsychiatryMedical University of LublinLublinPoland
  4. 4.Department of EndocrinologyMedical University of LublinLublinPoland
  5. 5.Department of Clinical NeuroscienceKarolinska Institutet, Section of Psychiatry at Karolinska University Hospital HuddingeStockholmSweden

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