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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects

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

Volume 25, Issue 42, 2018

Page: [5945 - 5957] Pages: 13

DOI: 10.2174/0929867325666180313113411

Price: $65

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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.

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


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