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Manipulating kynurenic acid levels in the brain - on the edge between neuroprotection and cognitive dysfunction.
MedLine Citation:
PMID:  23030614     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A number of neurodegenerative diseases have been associated with potentially neurotoxic alterations in the kynurenine pathway. Due to the potent inhibitory effect of kynurenic acid on glutamate receptor function, the potential use of the elevation of its concentrations in the brain in the protection against excitotoxic injury has earned an ever greater interest. The first strong preclinical achievements of protection in transgenic murine models of chronic neurodegenerative diseases by kynurenergic approaches have recently been published. Despite the remarkable neuroprotection provided by these molecules, the potential risk of interfering with cognitive functions when dealing with molecules capable of impairing glutamatergic and cholinergic transmission should always be considered. This issue is of particular interest in light of the high affinity of kynurenic acid towards the glycine site of NMDA receptors, the antagonism of which is known to recapitulate key behavioral features of schizophrenia. In the past decade, however, a number of other sites of action have been revealed, most of them being possible contributors of either the neuroprotective or the cognitive deteriorating effects of kynurenic acid. This paper reviews the current understanding about how kynurenic acid can influence cognitive functions in experimental animals, and discusses the possibility of exploiting the neuroprotective potential of kynurenic acid without impairing cognitive functions.
Authors:
Levente Szalardy; Denes Zadori; Jozsef Toldi; Ferenc Fulop; Peter Klivenyi; Laszlo Vecsei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-20
Journal Detail:
Title:  Current topics in medicinal chemistry     Volume:  -     ISSN:  1873-4294     ISO Abbreviation:  Curr Top Med Chem     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101119673     Medline TA:  Curr Top Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neurology, University of Szeged, H-6725 Szeged, Semmelweis u. 6, Hungary. vecsei.laszlo@med.u-szeged.hu.
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