Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects

Title:Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects

Volume: 25 Issue: 42

Author(s): Péter Hertelendy, József Toldi, Ferenc Fülöp and László Vécsei*

Affiliation:

• Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged,Hungary

Keywords: Kynurenine, stroke, ischemia, immunomodulation, kynurenine analogue, excitotoxicity.

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.

Cite this article as:

Hertelendy Péter, Toldi József, Fülöp Ferenc and Vécsei László *, Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects, Current Medicinal Chemistry 2018; 25 (42) . https://dx.doi.org/10.2174/0929867325666180313113411