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Endogenous Kynurenic Acid and Neurotoxicity

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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Urbańska, E.M., Chmiel-Perzyńska, I., Perzyński, A., Derkacz, M., Owe-Larsson, B. (2014). Endogenous Kynurenic Acid and Neurotoxicity. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_92

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