Title:Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects
Volume: 25
Issue: 42
关键词:
犬尿氨酸,中风,缺血,免疫调节,犬尿氨酸类似物,兴奋毒性。
摘要: 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.