Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects

Péter Hertelendy, J. Toldi, F. Fülöp, L. Vécsei

Research output: Contribution to journalReview article

Abstract

Ischemic stroke is one of the leading causes of mortality and permanent disability in developed countries. Stroke induces massive glutamate release, which in turn causes N-Methyl-D-aspartate (NMDA) receptor over-excitation and thus, calcium overload in neurons leading to cell death via apoptotic cascades. The kynurenine pathway is a complex enzymatic cascade of tryptophan catabolism, generating various neuroactive metabolites. One metabolite, kynurenic acid (KYNA), is a potent endogenous NMDA glutamate receptor antagonist, making it a possible therapeutic tool to decrease excitotoxicity and neuroinflammation. Recently, clinical investigations have shown that during the acute phase of ischemic stroke, kynurenine pathway is activated and peripheral levels of metabolites correlated with worse outcome. In this review, we set out to summarize the current literature on the connection of the kynurenine pathway and ischemic stroke and set a course for future investigations and potential drug development.

Original languageEnglish
Pages (from-to)5945-5957
Number of pages13
JournalCurrent medicinal chemistry
Volume25
Issue number42
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Kynurenine
Pharmaceutical Chemistry
Metabolites
Stroke
N-Methyl-D-Aspartate Receptors
Kynurenic Acid
Excitatory Amino Acid Antagonists
Cell death
N-Methylaspartate
Tryptophan
Neurons
Glutamic Acid
Developed Countries
Calcium
Cell Death
Pharmaceutical Preparations
Mortality

Keywords

  • excitotoxicity
  • immunomodulation
  • ischemia
  • Kynurenine
  • kynurenine analogue
  • stroke.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Ischemic Stroke and Kynurenines : Medicinal Chemistry Aspects. / Hertelendy, Péter; Toldi, J.; Fülöp, F.; Vécsei, L.

In: Current medicinal chemistry, Vol. 25, No. 42, 01.01.2018, p. 5945-5957.

Research output: Contribution to journalReview article

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