Abstract
Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting oligodendrocytes with sparing of axons until advanced stages of the disease. For this reason, most of the earliest experimental studies focused on the role of cytokines and chemokines at the site of oligodendrocytes loss and on the importance in MS pathogenesis of classical inflammatory mechanisms. As a result, several attempts to treat MS through reduction of the local inflammatory milieau have been performed, leading to the current “immunomodulatory” treatment of the disease. However, more recently the importance of axonal loss and neurodegeneration even in the earliest stages of MS has been also recognized, and additional or concomitant players have been therefore searched. Evidence is now increasing that excessive glutamate is released at the site of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating leukocytes and activated microglia. These observations are no longer simply preclinical results obtained in the MS animal model, i.e. experimental allergic encephalomyelitis, but have already been partially confirmed by post-mortem studies and in vivo analysis in MS patients, thus raising the possibility that modulation of glutamate release and transport as well as receptors blockade might be relevant targets for the development of future therapeutic interventions.
Keywords: Glutamate, multiple sclerosis, neurodegeneration, inflammation, demyelination, post-mortem studies, immunomodulatory, encephalomyelitis, glutamatergic
Current Medicinal Chemistry
Title: Glutamate and Multiple Sclerosis
Volume: 19 Issue: 9
Author(s): M. Frigo, M. G. Cogo, M. L. Fusco, M. Gardinetti and B. Frigeni
Affiliation:
Keywords: Glutamate, multiple sclerosis, neurodegeneration, inflammation, demyelination, post-mortem studies, immunomodulatory, encephalomyelitis, glutamatergic
Abstract: Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting oligodendrocytes with sparing of axons until advanced stages of the disease. For this reason, most of the earliest experimental studies focused on the role of cytokines and chemokines at the site of oligodendrocytes loss and on the importance in MS pathogenesis of classical inflammatory mechanisms. As a result, several attempts to treat MS through reduction of the local inflammatory milieau have been performed, leading to the current “immunomodulatory” treatment of the disease. However, more recently the importance of axonal loss and neurodegeneration even in the earliest stages of MS has been also recognized, and additional or concomitant players have been therefore searched. Evidence is now increasing that excessive glutamate is released at the site of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating leukocytes and activated microglia. These observations are no longer simply preclinical results obtained in the MS animal model, i.e. experimental allergic encephalomyelitis, but have already been partially confirmed by post-mortem studies and in vivo analysis in MS patients, thus raising the possibility that modulation of glutamate release and transport as well as receptors blockade might be relevant targets for the development of future therapeutic interventions.
Export Options
About this article
Cite this article as:
Frigo M., G. Cogo M., L. Fusco M., Gardinetti M. and Frigeni B., Glutamate and Multiple Sclerosis, Current Medicinal Chemistry 2012; 19 (9) . https://dx.doi.org/10.2174/092986712799462559
DOI https://dx.doi.org/10.2174/092986712799462559 |
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
-
Biological Drugs in Guillain-Barré Syndrome: An Update
Current Neuropharmacology Cyclooxygenases in the Central Nervous System: Implications for Treatment of Neurological Disorders
Current Pharmaceutical Design Nasal Drug Delivery System-Factors Affecting and Applications
Current Drug Therapy Peroxisome Proliferator-Activated Receptors and the Control of Inflammation Update
Medicinal Chemistry Reviews - Online (Discontinued) Natural Tregs in Systemic Lupus Erythematosus
Current Immunology Reviews (Discontinued) Antiviral Drug Discovery Targeting to Viral Proteases
Current Pharmaceutical Design Microwave Assisted Organic Synthesis of Heterocycles in Aqueous Media: Recent Advances in Medicinal Chemistry
Medicinal Chemistry Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation
Current Drug Targets mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems
Current Drug Targets Insights into Immunophilin Structure and Function
Current Medicinal Chemistry GEMSP: A New Therapeutic Approach to Multiple Sclerosis
Central Nervous System Agents in Medicinal Chemistry Editorial [Hot Topic:Controlling Autoimmunity by Modulating the Function of Autoantigen-Specific T Cells (Guest Editor: Andrew D. Weinberg)]
Current Drug Targets - Inflammation & Allergy Transmissibility and Epidemicity of COVID-19 in India: A Case Study
Recent Advances in Anti-Infective Drug Discovery Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents
Recent Patents on Inflammation & Allergy Drug Discovery Peroxisome Proliferator-Activated Receptor Agonists as Potential Therapeutic Agents in Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry Therapeutic Approach for Neuronal Disease by Regulating Reninangiotensin System
Current Hypertension Reviews Identification of Novel 5,6-Dimethoxyindan-1-one Derivatives as Antiviral Agents
Medicinal Chemistry Pathogenic Bacterial Proteins and their Anti-Inflammatory Effects in the Eukaryotic Host
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Anti-Arthritic Effects of Immunomodulatory Peptide Injected in Joints
Current Drug Delivery The Modulation of Pain by Metabotropic Glutamate Receptors 7 and 8 in the Dorsal Striatum
Current Neuropharmacology