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
-
Image Fusion of Diagnostic Ultrasound with Other Modalities
Current Medical Imaging Anti-cancer Drug Discovery: Update and Comparisons in Yeast, Drosophila, and Zebrafish
Current Molecular Pharmacology Challenges in the Design of Clinically Useful Brain-targeted Drug Nanocarriers
Current Medicinal Chemistry CDC25A: A Rebel Within the CDC25 Phosphatases Family?
Anti-Cancer Agents in Medicinal Chemistry Effects of Diet-Derived Molecules on the Tumor Microenvironment
Current Angiogenesis (Discontinued) Friend or Foe: UCHL3 Mediated Carcinogenesis and Current Approaches in Small Molecule Inhibitors’ Development
Current Medicinal Chemistry Histone Deacetylases: Anti-Angiogenic Targets in Cancer Therapy
Current Cancer Drug Targets Oncolytic Viruses: The Best is Yet to Come
Current Cancer Drug Targets Synergistic Effect of Immunotherapy and Chemotherapy in Cancers: Perspective in High Grade Glioma Treatment
Letters in Drug Design & Discovery Nanocarriers for Effective Brain Drug Delivery
Current Topics in Medicinal Chemistry Tumour Re-Differentiation Effect of Retinoic Acid: A Novel Therapeutic Approach for Advanced Thyroid Cancer
Current Pharmaceutical Design Heterocyclic Curcumin Derivatives of Pharmacological Interest: Recent Progress
Current Topics in Medicinal Chemistry Antiviral Drugs that Target Cellular Proteins May Play Major Roles in Combating HIV Resistance
Current Pharmaceutical Design Nano-constructed Carriers Loaded With Antioxidant: Boon For Cardiovascular System
Current Pharmaceutical Design The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review
Anti-Cancer Agents in Medicinal Chemistry Hypoxia-inducible Factor (HIF) in Hormone Signaling During Health and Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry EGFR-Targeted Therapy in Malignant Glioma: Novel Aspects and Mechanisms of Drug Resistance
Current Molecular Pharmacology Glucose Oncometabolism of Esophageal Cancer
Anti-Cancer Agents in Medicinal Chemistry Cancer Cell Reprogramming: Stem Cell Differentiation Stage Factors and An Agent Based Model to Optimize Cancer Treatment
Current Pharmaceutical Biotechnology Review of the Contribution of Radiolabelled Tracers for Tumour Cell Status Imaging
Current Medical Imaging