Abstract
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.
Keywords: Excitotoxicity, Cognitive functions, Glutamate, Glycine co-agonist site, Kynurenic acid, Neuroprotection
Current Topics in Medicinal Chemistry
Title:Manipulating Kynurenic Acid Levels in the Brain – On the Edge Between Neuroprotection and Cognitive Dysfunction
Volume: 12 Issue: 16
Author(s): Levente Szalardy, Denes Zadori, Jozsef Toldi, Ferenc Fulop, Peter Klivenyi and Laszlo Vecsei
Affiliation:
Keywords: Excitotoxicity, Cognitive functions, Glutamate, Glycine co-agonist site, Kynurenic acid, Neuroprotection
Abstract: 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.
Export Options
About this article
Cite this article as:
Szalardy Levente, Zadori Denes, Toldi Jozsef, Fulop Ferenc, Klivenyi Peter and Vecsei Laszlo, Manipulating Kynurenic Acid Levels in the Brain – On the Edge Between Neuroprotection and Cognitive Dysfunction, Current Topics in Medicinal Chemistry 2012; 12 (16) . https://dx.doi.org/10.2174/1568026611209061797
DOI https://dx.doi.org/10.2174/1568026611209061797 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Potential of Antibiotics for the Treatment and Management of Parkinson's Disease: An Overview
Current Drug Research Reviews Blood-Brain Barrier and Breast Cancer Resistance Protein: A Limit to the Therapy of CNS Tumors and Neurodegenerative Diseases
Anti-Cancer Agents in Medicinal Chemistry The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View
Current Alzheimer Research Glutathione Peroxidase: A Potential Marker for the Most Common Diseases and Disorders
Recent Patents on Biomarkers Coumarins as Promising Scaffold for the Treatment of Age-related Diseases – An Overview of the Last Five Years
Current Topics in Medicinal Chemistry Sirtuins: Possible Clinical Implications in Cardio and Cerebrovascular Diseases
Current Drug Targets Oxidant/Antioxidant Imbalance and the Risk of Alzheimer's Disease
Current Alzheimer Research Editorial (Thematic Selection: Strategies of Current Drugs and Alternative Treatments for Neurodegenerative Diseases)
Current Neuropharmacology Lipoic Acid, a Lead Structure for Multi-Target-Directed Drugs for Neurodegeneration
Mini-Reviews in Medicinal Chemistry Defects in RNA Metabolism links FTD and ALS Pathogenesis: TDP-43, FUS, and C9orf72
Current Enzyme Inhibition Alkaloids from Cyanobacteria with Diverse Powerful Bioactivities
Mini-Reviews in Medicinal Chemistry Tau Protein Aggregation in Alzheimer's Disease: Recent Advances in the Development of Novel Therapeutic Agents
Current Pharmaceutical Design Anti-inflammatory and Immune Therapy for Alzheimers Disease: Current Status and Future Directions
Current Neuropharmacology RNAi Applications in Therapy Development for Neurodegenerative Disease
Current Pharmaceutical Design Pathogenic Mechanisms and Therapeutic Strategies in Spinobulbar Muscular Atrophy
CNS & Neurological Disorders - Drug Targets Signaling Mechanisms Underlying Aβ Toxicity: Potential Therapeutic Targets for Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Magnetic Resonance-Based Metabolomics for Understanding Neurological Disorders: Current Status and Statistical Considerations
Current Metabolomics Editorial (Thematic Issue: MiRNAcles in the Brain: What to Wish and What to Fear)
CNS & Neurological Disorders - Drug Targets Experimental Research on Nitric Oxide and the Therapy of Alzheimer Disease: A Challenging Bridge
CNS & Neurological Disorders - Drug Targets The Impact of Natural Compounds on the Treatment of Neurodegenerative Diseases
Current Organic Chemistry