Multiple Sclerosis: Bench to Bedside: Global Perspectives on a Silent Killer (Advances in Experimental Medicine and Biology Book 958)

"Multiple Sclerosis (MS) is one of the main causes of disability in young adult population. The estimated burden of the disease worldwide is about three million people. The pathogenic mechanism of MS involves both auto immune and degenerative processes. These two mechanisms are thought to determine a combination of events leading to several clinical pattern of disease onset and course. Multiple Sclerosis: Bench to Bedside provides the most up-to-date and concise reviews on the critical issues of multiple sclerosis from around the world. This book is written by leaders and experts in the field of multiple sclerosis research and is divided into easy to read sections. Section I focuses on basic science aspects of Multiple Sclerosis, including potential biomarkers, molecular biology, heat shock proteins, oxidative stress, genetic and epigenetics. Section II focuses on clinical and epidemiological aspects of Multiple Sclerosis, including remyelination therapy, neuroplasticity-based technologies and interventions. This is an important reference book and a must-read for Postgraduate Medical Scholars, Basic Science Researchers and Neurologists in Clinical Practice"--Publisher's description Preface 6 Contents 7 1: Extracellular Vesicles in Multiple Sclerosis as Possible Biomarkers: Dream or Reality? 9 1.1 Introduction 10 1.2 Origins of Extracellular Vesicle 11 1.3 Mechanism of Interaction Between Extracellular Vesicles and Target Cells 12 1.4 Extracellular Vesicles in the Central Nervous System 12 1.5 Extracellular Vesicle Role in Multiple Sclerosis 12 1.6 Conclusion 13 References 14 2: Manipulation of Oxygen and Endoplasmic Reticulum Stress Factors as Possible Interventions for Treatment of Multiple Sclerosis: Evidence for and Against 18 2.1 Introduction 19 2.2 Oxidative and ER Stress in MS Pathology 20 2.3 HBOT and MS: Clinical and Patient Perspectives 24 2.4 ER Targeted Therapeutics and MS 26 2.4.1 Effect of HBOT on Cell Function and Gene Expression 26 2.4.2 Neural UPR Sensor Genes 28 2.5 Conclusion 30 References 30 3: Heat Shock Proteins in Multiple Sclerosis 35 3.1 Introduction 36 3.2 Heat Shock Proteins 36 3.3 Classification 37 3.3.1 HSP60 38 3.3.2 HSP70 38 3.3.3 HSP90 39 3.3.4 Small HSPs 39 3.3.4.1 Alpha B-Crystallin 39 3.3.4.2 HSP27 39 3.3.5 Extracellular Role of HSP Molecules 40 3.4 HSPs in MS Pathogenesis 40 3.5 Conclusion 46 References 46 4: Meaning of Self in Multiple Sclerosis: Implications for Treatment and Rehabilitation 49 4.1 Introduction 50 4.2 Self-Esteem in MS 51 4.3 Self-Efficacy in MS 54 4.4 Self-Management in MS 56 4.5 Conclusion 57 References 58 5: Multiple Sclerosis and EIF2B5: A Paradox or a Missing Link 62 5.1 Introduction 63 5.2 MS and EIF2B5 65 5.3 Conclusion 67 References 68 6: Molecular Genetic and Epigenetic Basis of Multiple Sclerosis 70 6.1 Introduction 71 6.2 JAK-STAT Pathway 72 6.2.1 JAK/STAT Pathway and MS 73 6.3 NF-κB Pathway 74 6.3.1 NF-κB and Multiple Sclerosis 76 6.4 Notch Signaling 78 6.4.1 Notch Signaling and MS 78 6.5 Wnt Signaling 81 6.5.1 Canonical Wnt Signaling and MS 81 6.5.2 MAPK-p38 and MS 83 6.5.3 PI3K and MS 84 6.6 Epigenetic Mechanisms 84 6.6.1 DNA Methylation 84 6.6.2 Post-translational Histone Modifications 85 6.6.3 miRNA-Associated Post- 85 6.7 Role of Epigenetics Changes Associated with MS 85 6.7.1 DNA Methylation in Pathogenesis of MS 86 6.7.2 Histone Modifications in Pathogenesis of MS 87 6.7.3 Histone Deacetylase (HDAC) Inhibitors 87 6.8 miRNAs and Multiple Sclerosis 88 6.8.1 Environmental Risk Factors and Epigenetic of MS 89 6.8.2 Vitamin D Deficiency 89 6.8.3 Smoking 89 6.8.4 Epstein–Barr Virus (EBV) 90 References 90 7: Role of Oligodendrocyte Dysfunction in Demyelination, Remyelination and Neurodegeneration in Multiple Sclerosis 96 7.1 Introduction 97 7.2 Demyelination in Multiple Sclerosis – White Matter and Grey Matter Pathology and Association Between Pathological, MRI and Clinical Findings 99 7.2.1 Focal White Matter Demyelination 99 7.2.2 Diffuse White Matter Demyelination 100 7.2.3 Grey Matter Demyelination 101 7.3 Oligodendrocyte Dysfunction in Multiple Sclerosis 103 7.3.1 Oligodendrocyte Progenitor Cells and Oligodendrocytes During CNS Development 103 7.3.2 Role of Oligodendrocyte in Myelination and Trophic Support of Axons in Humans 104 7.3.3 Oligodendroglial Dysfunction and Demyelination in Multiple Sclerosis 106 7.3.4 Oligodendrocytes and Neurodegeneration in MS 107 7.3.5 Role of Oligodendrocyte in CNS Remyelination and Regeneration in MS 108 7.4 Oligodendrocyte Progenitor Cells (OPCs) Dysfunction and Potential Therapeutic Targets for remyelinating Therapies in MS 110 7.4.1 Depletion of OPCs 110 7.4.2 Impaired Migration 111 7.4.3 Chemokines 111 7.4.4 Impaired Differentiation of OPCs in MS 112 7.4.5 Olig 2 Factor 112 7.4.6 LINGO-1 Signaling 112 7.4.7 Canonical Notch Signaling 112 7.4.8 Wnt Signaling 113 7.4.9 RXR Signaling 113 7.4.10 Endocrine Targets 114 7.4.11 Other Factors That Influence OPCs Migration and Differentiation 115 7.5 Oligodendrocytes as Immunomodulatory Cells in MS 115 7.6 Promoting Remyelination – Perspectives for Regenerative Therapies in MS 116 7.6.1 S1P Modulation Agents 116 7.6.2 Alemtuzumab 117 7.6.3 Dimethyl Fumarate 117 7.6.4 Human Monoclonal IgM Antibody 22 118 7.6.5 Glatiramer Acetate (GA) 118 7.6.6 Laquinimod (LQ) 119 7.7 Conclusion 119 References 119 8: Clinical Neurophysiology of Multiple Sclerosis 133 8.1 Introduction 134 8.2 Evoked Potentials in Multiple Sclerosis 134 8.2.1 The EP Score 135 8.3 Autonomic Dysfunction in Multiple Sclerosis 137 8.4 Sleep Disorders in Multiple Sclerosis 139 8.5 Conclusion 140 References 140 9: Multiple Sclerosis Epidemiology in Europe 144 9.1 Introduction 145 9.2 Epidemiology in Europe 146 9.2.1 The Nordic Region 156 9.2.2 The British Isles 156 9.2.3 Central European Countries 156 9.2.4 Iberian Peninsula 157 9.2.5 Italy 157 9.2.6 South East Europe 158 9.2.7 Eastern Europe 158 9.3 Conclusion 158 References 159 10: Timing of Future Remyelination Therapies and Their Potential to Stop Multiple Sclerosis Progression 163 10.1 Introduction 164 10.2 Neuropathology of MS 164 10.3 Potential Treatment Strategies of MS 164 10.3.1 Remyelination 165 10.3.2 Naturally Occurring Human Monoclonal Antibodies 165 10.4 MS Phases (Sub-Phenotypes) 166 10.5 Management of MS 166 10.5.1 Treatment of Acute MS Relapses 166 10.5.2 Prevention of Acute MS Relapses 167 10.5.3 Management of Progressive Phase of MS 167 10.5.4 Future Treatment Directions of Remyelination 168 10.6 Conclusion 169 References 169 11: Neuroplasticity-Based Technologies and Interventions for Restoring Motor Functions in Multiple Sclerosis 173 11.1 Introduction 174 11.2 Functional Recovery in Multiple Sclerosis 175 11.3 Principles of Use-Dependent Neuroplasticity 176 11.4 Robotics 176 11.4.1 Gait Training with Robotics 177 11.4.2 Upper Limb Motor Training with Robotics 179 11.5 Constraint-Induced Movement Therapy 181 11.5.1 Virtual Reality (VR) 182 11.6 Non-invasive Brain Stimulation (NIBS) 183 11.7 Conclusion 184 References 184 Index 188 Multiple Sclerosis (MS) is one of the main causes of disability in young adult population. The estimated burden of the disease worldwide is about three million people. The pathogenic mechanism of MS involves both auto immune and degenerative processes. These two mechanisms are thought to determine a combination of events leading to several clinical pattern of disease onset and course. Multiple Sclerosis: Global Perspectives on a Silent Killer provides the most up-to-date and concise reviews on the critical issues of multiple sclerosis from around the world. This book is written by leaders and experts in the field of multiple sclerosis research and is divided into easy to read sections. Section I focuses on basic science aspects of Multiple Sclerosis, including potential biomarkers, molecular biology, heat shock proteins, oxidative stress, genetic and epigenetics. Section II focuses on clinical and epidemiological aspects of Multiple Sclerosis, including remyelination therapy, neuroplasticity-based technologies and interventions. This is an important reference book and a must-read for Undergraduate and Postgraduate Medical Scholars, Basic Science Researchers, Neurology Fellows, Neurology Residents and Neurologists in Clinical Practice Front Matter....Pages i-viii Extracellular Vesicles in Multiple Sclerosis as Possible Biomarkers: Dream or Reality?....Pages 1-9 Manipulation of Oxygen and Endoplasmic Reticulum Stress Factors as Possible Interventions for Treatment of Multiple Sclerosis: Evidence for and Against....Pages 11-27 Heat Shock Proteins in Multiple Sclerosis....Pages 29-42 Meaning of Self in Multiple Sclerosis: Implications for Treatment and Rehabilitation....Pages 43-55 Multiple Sclerosis and EIF2B5: A Paradox or a Missing Link....Pages 57-64 Molecular Genetic and Epigenetic Basis of Multiple Sclerosis....Pages 65-90 Role of Oligodendrocyte Dysfunction in Demyelination, Remyelination and Neurodegeneration in Multiple Sclerosis....Pages 91-127 Clinical Neurophysiology of Multiple Sclerosis....Pages 129-139 Multiple Sclerosis Epidemiology in Europe....Pages 141-159 Timing of Future Remyelination Therapies and Their Potential to Stop Multiple Sclerosis Progression....Pages 161-170 Neuroplasticity-Based Technologies and Interventions for Restoring Motor Functions in Multiple Sclerosis....Pages 171-185 Back Matter....Pages 187-188