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
-
TNF α Signaling Beholds Thalidomide Saga: A Review of Mechanistic Role of TNF-α Signaling Under Thalidomide
Current Topics in Medicinal Chemistry Natural Antibodies: Protecting Role of IgM in Glioblastoma and Brain Tumours
Current Pharmaceutical Design Cancer Cell Reprogramming: Stem Cell Differentiation Stage Factors and An Agent Based Model to Optimize Cancer Treatment
Current Pharmaceutical Biotechnology Thioureas as Building Blocks for the Generation of Heterocycles and Compounds with Pharmacological Activity: An Overview
Mini-Reviews in Organic Chemistry The Glioblastoma Problem: Targeting by Combined Medicinal Chemistry Approaches
Current Medicinal Chemistry Trends in Malignant Glioma Monoclonal Antibody Therapy
Current Cancer Therapy Reviews The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Recent Patents on Anti-Cancer Drug Discovery Individualized Treatment Planning in Oncology: Role of PET and Radiolabelled Anticancer Drugs in Predicting Tumour Resistance
Current Pharmaceutical Design Inhibiting the “Undruggable” RAS/Farnesyltransferase (FTase) Cancer Target by Manumycin-related Natural Products
Current Medicinal Chemistry Recent Advances in Pretargeted Radioimmunotherapy
Current Medicinal Chemistry Conventional Anticancer Therapeutics and Telomere Maintenance Mechanisms
Current Pharmaceutical Design Design and Application of Magnetic-Based Theranostic Nanoparticle Systems
Recent Patents on Biomedical Engineering (Discontinued) Biocompatible Targeting Hydrogels for Breast Cancer Treatment
Mini-Reviews in Medicinal Chemistry Recent Progress in Anticancer Agents Incorporating Pyrazole Scaffold
Mini-Reviews in Medicinal Chemistry Peptidergic Regulation of Pheochromocytoma
Current Pharmacogenomics Hypoxic Radiosensitizers and Hypoxic Cytotoxins in Radiation Oncology
Current Medicinal Chemistry - Anti-Cancer Agents Clinical and Therapeutic Challenges when Psychiatric Disorders Occur in Neurological Diseases: A Narrative Review
Current Psychiatry Research and Reviews Self Assembling Polymers as Polymersomes for Drug Delivery
Current Pharmaceutical Design The Ever Changing Treatments for Tumors of the Central Nervous System
Current Cancer Therapy Reviews 1,2,3-Triazine Scaffold as a Potent Biologically Active Moiety: A Mini Review
Mini-Reviews in Medicinal Chemistry