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Kynurenines in Neurodegenerative Disorders: Therapeutic Consideration

  • Péter Klivényi
  • József Toldi
  • László Vécsei
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 541)

Abstract

The kynurenine pathway is a major route for the conversion of tryptophane to NAD and NADP (Figure 1), leading to production of a number of biologically active molecules with neuroactive properties. During the last decades, the interest in kynurenines has been emerged as two major metabolites of this pathway, quinolinic acid (QUIN) and kynurenic acid (KYNA), act on glutamate receptors. QUIN was shown to be an agonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptors. KYNA was shown to be an antagonist the same NMDA receptors with a high affinity to the glycin coagonist site. The NMDA receptor activation has been implicated in many neurological disorders such as stroke, brain injury, Parkinson’s disease, Huntington’s disease and multiple sclerosis. The receptor antagonists reduce the excitotoxic damage both in vivo1,2,3 and in vitro4 and could be used against neurodegenerative disorders. However the classical antagonists have some adverse effects, that limit their clinical use such as memory and learning impairment, psychosis and cell deaths.5 Influencing the kynurenine pathway provides an option to increase the neuroprotective capacity and decrease the concentration of neurotoxic metabolites. On the other hand, the impariment of kynurenine system has been implicated in several neurological disorders such as stroke, brain injury, Parkinson’s disease, Huntington’s disease and multiple sclerosis.

Keywords

NMDA Receptor Quinolinic Acid Kynurenic Acid Kynurenine Pathway Excitatory Amino Acid Receptor 
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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© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Péter Klivényi
    • 1
  • József Toldi
    • 2
  • László Vécsei
    • 3
  1. 1.Department of NeurologyUniversity of SzegedSzegedHungary
  2. 2.Department of Comparative PhysiologyUniversity of SzegedSzegedHungary
  3. 3.Neurology Research Group of the Hungarian Academy of Sciences and University of SzegedSzegedHungary

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