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.
Current Medicinal Chemistry
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/0929867325666180313113411 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Nanomedicine for Gene Delivery for the Treatment of Cardiovascular Diseases
Current Gene Therapy Dysregulation of LncRNAs in Placenta and Pathogenesis of Preeclampsia
Current Drug Targets Therapeutic Perspectives on Pancreatic Cancer
Current Cancer Drug Targets Converging Perturbed Microvasculature and Microglial Clusters Characterize Alzheimer Disease Brain
Current Alzheimer Research Hypothyroidism and Atherosclerosis-Possible Implication of the Renin-Angiotensin System
Current Hypertension Reviews Beneficial Effects of Traditional Chinese Medicine on the Treatment of Osteoporosis on Ovariectomised Rat Models
Current Drug Targets Editorial
Recent Patents on CNS Drug Discovery (Discontinued) Cardioprotection Against Ischemia/Reperfusion Injury and Chromogranin ADerived Peptides
Current Medicinal Chemistry Increased Exercise Favorably Modifies Coronary Artery Disease and Peripheral Arterial Disease Outcomes
Current Vascular Pharmacology Cardiovascular Disease in Diabetes
Mini-Reviews in Medicinal Chemistry Anti-Atherosclerotic Molecules Targeting Oxidative Stress and Inflammation
Current Pharmaceutical Design Preface
Cardiovascular & Hematological Disorders-Drug Targets Rational Autologous Cell Sources For Therapy of Heart Failure - Vehicles and Targets For Gene and RNA Therapies
Current Gene Therapy Meet Our Editorial Board Member
Cardiovascular & Hematological Disorders-Drug Targets Protective Effect of Notoginsenoside R1 on an APP/PS1 Mouse Model of Alzheimer's Disease by Up-Regulating Insulin Degrading Enzyme and Inhibiting Aβ Accumulation
CNS & Neurological Disorders - Drug Targets Effects of Acute and Chronic Biomechanical Strain on Human Cerebral Endothelial Cells in Altering their Proteome Profile
Current Proteomics Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration
Current Molecular Medicine Clinical Applicability of Conditioning Techniques in Ischemia-Reperfusion Injury: A Review of the Literature
Current Cardiology Reviews Impacts of Nanoparticles on Cardiovascular Diseases: Modulating Metabolism and Function of Endothelial Cells
Current Drug Metabolism Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI) Patients are Characterized by Increased BDNF Serum Levels
Current Alzheimer Research