Abstract
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), characterized by inflammation, demyelination and axonal loss underlying progressive clinical disability. The chronic inflammatory tissue damage involving myelin and axons is driven by autoreactive T cells and represents a key mechanism in the immunopathogenesis of MS. Over the last few years, evidence from MS and experimental models of neuroinflammation has suggested that autoimmune responses could exert neuroprotective effects through the release of neurotrophins by autoreactive T cells. Specifically, the role of the Brain-derived neurotrophic factor (BDNF) in facilitating brain tissue repair in experimental traumatic injury has been well recognized. Support for this hypothesis comes from recent studies showing that glatiramer acetate, a currently approved treatment for MS, promotes the expansion of T cell clones crossing the blood-brain barrier and releasing BDNF in situ. A small subset of autoreactive T cells expresses the high-affinity full-length receptor for BDNF (TrkB-TK) in the periphery. In MS patients, T cells show reduced susceptibility to activation-induced apoptosis, a crucial mechanism eliminating autoreactive T clones and contributing to peripheral immunologic tolerance. These findings suggest the existence of a dual effect exerted by BDNF, which not only provides neuroprotection in the CNS but also promotes the survival of autoreactive T cells through an autocrine/paracrine loop. The aim of this review is to discuss the neuroprotective effects of currently approved immunomodulatory treatments for MS and their role in regulating neurotrophin production. We will also describe novel therapeutic strategies arising from new insights on “neuroprotective autoimmunity”.
Keywords: Autoimmunity, BDNF, immunomodulatory drugs, multiple sclerosis, neuroinflammation, neuroprotection, TrkB, central nervous system (CNS), immunopathogenesis
Current Medicinal Chemistry
Title: Neuroinflammation and Neuroprotection: An Update on (Future) Neurotrophin-Related Strategies in Multiple Sclerosis Treatment
Volume: 18 Issue: 12
Author(s): L. De Santi, G. Polimeni, S. Cuzzocrea, E. Esposito, E. Sessa, P. Annunziata and P. Bramanti
Affiliation:
Keywords: Autoimmunity, BDNF, immunomodulatory drugs, multiple sclerosis, neuroinflammation, neuroprotection, TrkB, central nervous system (CNS), immunopathogenesis
Abstract: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), characterized by inflammation, demyelination and axonal loss underlying progressive clinical disability. The chronic inflammatory tissue damage involving myelin and axons is driven by autoreactive T cells and represents a key mechanism in the immunopathogenesis of MS. Over the last few years, evidence from MS and experimental models of neuroinflammation has suggested that autoimmune responses could exert neuroprotective effects through the release of neurotrophins by autoreactive T cells. Specifically, the role of the Brain-derived neurotrophic factor (BDNF) in facilitating brain tissue repair in experimental traumatic injury has been well recognized. Support for this hypothesis comes from recent studies showing that glatiramer acetate, a currently approved treatment for MS, promotes the expansion of T cell clones crossing the blood-brain barrier and releasing BDNF in situ. A small subset of autoreactive T cells expresses the high-affinity full-length receptor for BDNF (TrkB-TK) in the periphery. In MS patients, T cells show reduced susceptibility to activation-induced apoptosis, a crucial mechanism eliminating autoreactive T clones and contributing to peripheral immunologic tolerance. These findings suggest the existence of a dual effect exerted by BDNF, which not only provides neuroprotection in the CNS but also promotes the survival of autoreactive T cells through an autocrine/paracrine loop. The aim of this review is to discuss the neuroprotective effects of currently approved immunomodulatory treatments for MS and their role in regulating neurotrophin production. We will also describe novel therapeutic strategies arising from new insights on “neuroprotective autoimmunity”.
Export Options
About this article
Cite this article as:
De Santi L., Polimeni G., Cuzzocrea S., Esposito E., Sessa E., Annunziata P. and Bramanti P., Neuroinflammation and Neuroprotection: An Update on (Future) Neurotrophin-Related Strategies in Multiple Sclerosis Treatment, Current Medicinal Chemistry 2011; 18 (12) . https://dx.doi.org/10.2174/092986711795496881
DOI https://dx.doi.org/10.2174/092986711795496881 |
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
-
Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story
Current Chemical Biology Mesenchymal Stem Cells: A New Generation of Therapeutic Agents as Vehicles in Gene Therapy
Current Gene Therapy Natural Products as Anti-Invasive and Anti-Metastatic Agents
Current Medicinal Chemistry Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions
Current Cancer Drug Targets Cellular Uptake and Organ Accumulation of Amphipolar Metallocorroles with Cytoprotective and Cytotoxic Properties
Anti-Cancer Agents in Medicinal Chemistry Molecular Analysis of the In Vivo Metabolism and Biodistribution of Metabolically and Non-Metabolically Activated Combi-Molecules of the Triazene Class
Drug Metabolism Letters Electrochemical Cell-based Biosensors for Biomedical Applications
Current Topics in Medicinal Chemistry A Network Biology Approach for Assessing the Role of Pathologic Adipose Tissues in Insulin Resistance Using Meta-analysis of Microarray Datasets
Current Genomics Nanoparticles in Melanoma
Current Medicinal Chemistry A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells
Current Alzheimer Research Recent Developments in the Mechanism of Anticancer Agents Based on Electron Transfer, Reactive Oxygen Species and Oxidative Stress
Anti-Cancer Agents in Medicinal Chemistry Pharmacological Strategies that Affect HIF-1 in the Ischemic Brain: Focus on Hydroxylases Activity and Protein Kinase Pathways
Current Signal Transduction Therapy The Role of Circulating Endothelial Progenitor Cells in Tumor Angiogenesis
Current Stem Cell Research & Therapy Influence of Trishomocubanes on Sigma Receptor Binding of N-(1-Benzylpiperidin- 4-yl)-4-[123I]iodobenzamide In Vivo in the Rat Brain
Medicinal Chemistry Immunoregulatory and Effector Activities of Nitric Oxide and Reactive Nitrogen Species in Cancer
Current Medicinal Chemistry Breast Cancer: Current Developments in Molecular Approaches to Diagnosis and Treatment
Recent Patents on Anti-Cancer Drug Discovery Editorial (Thematic Issue: Systems and Network Biology in Pharmaceutical Drug Discovery)
Current Pharmaceutical Design In vivo behavior and Safety of Lapatinib-Incorporated Lipid Nanoparticles
Current Pharmaceutical Biotechnology Emerging Features in the Regulation of MMP-9 Gene Expression for the Development of Novel Molecular Targets and Therapeutic Strategies
Current Drug Targets - Inflammation & Allergy Oncolytic Virus Therapy - Foreword
Current Cancer Drug Targets