Note: Intro -- Foreword -- Preface -- Contents -- Chapter 1: Introduction -- 1.1 Overview of the Book -- 1.2 Biological Properties of Schwann Cells During Development, Maturation, and Axonal Degeneration and Regeneration (Chaps. 2, 3, 4, and 5) -- 1.3 Schwann Cell Abnormalities in the Pathogenesis of Peripheral Neuropathies (Chaps. 6, 7, 8, and 9) -- 1.4 Spontaneously Immortalized Schwann Cell Lines from Adult Rodents for the Study of Peripheral Nerve Degeneration and Regeneration (Chap. 10) -- 1.5 Conclusion -- References -- Chapter 2: Recent Insights into Molecular Mechanisms That Control Growth Factor Receptor-Mediated Schwann Cell Morphological Changes During Development -- 2.1 Introduction -- 2.2 Molecular Processes of Migration, the Hallmark of Cell Morphological Changes, in Schwann Cell Lineage Cells -- 2.2.1 Neuregulin-1 (NRG1) Promotes Migration -- 2.2.2 Antagonistic Regulation of Migration by Neurotrophins -- 2.2.3 Insulin-Like Growth Factor 1 (IGF-1) Promotes Migration -- 2.2.4 Glial Cell Line-Derived Neurotrophic Factor (GDNF) Promotes Migration -- 2.2.5 Growth Arrest-Specific 6 (Gas6) Promotes Migration -- 2.2.6 Promotion of Migration Through the Low Density Lipoprotein (LDL) Receptor-Related Protein-1 (LRP1) -- 2.2.7 Promotion of Migration Through the Erythropoietin Receptor -- 2.2.8 Regulation of Migration Through Semaphorin Signaling -- 2.2.9 Regulation of Migration Through Ephrin Signaling -- 2.3 Molecular Processes of Myelination of Axons by Schwann Cells -- 2.3.1 NRG1 Promotes Myelination -- 2.3.2 Control of Myelination Through a Possible Cyclic AMP-Producing G Protein-Coupled Receptor 126 (GPR126) -- 2.3.3 Antagonistic Regulation of Myelination by Neurotrophins -- 2.3.4 Promotion of Myelination by IGF-1 and Its Inhibition by Platelet-Derived Growth Factor (PDGF) -- 2.3.5 GDNF Promotes Myelination -- 2.4 Conclusions and Perspectives. , References -- Chapter 3: Membrane Skeleton in Schmidt-Lanterman Incisure in Schwann Cells of the Peripheral Nervous System -- 3.1 Membrane Skeleton and Protein 4.1 Families -- 3.2 Structure of Schmidt-Lanterman Incisure (SLI) -- 3.3 Protein 4.1G and MAGUK Proteins for Cell-Cell Adhesion -- 3.4 Protein 4.1G and Cell Adhesion Molecule (CADM) Families -- 3.5 Size Determination of SLI by Protein 4.1G -- 3.6 Other MAGUK Proteins in Schwann Cells -- 3.7 Src Kinase Family Protein in SLI -- 3.8 Interaction of Src with MPP6 in Schwann Cells -- 3.9 Involvement of Src with Other Adhesion Molecules and Membrane Skeletal Components in Schwann Cells -- 3.10 Phosphorylation State of Src in Schwanomma -- 3.11 Involvement of Src in Schwann Cell SLIs Under Development and Wallerian Degeneration -- 3.12 Concluding Remarks -- References -- Chapter 4: Schwann Cell-Axon Interactions: The Molecular and Metabolic Link Between Schwann Cells and Axons -- 4.1 Introduction -- 4.2 Structural Interactions Between Schwann Cells and Axons -- 4.3 Axonal Signaling for Modulation of Schwann Cell Behavior -- 4.4 Metabolic Link Between Schwann Cells and Axons -- 4.5 Conclusions and Perspectives -- References -- Chapter 5: Schwann Cell-Dependent Regulation of Peripheral Nerve Injury and Repair -- Abbreviations -- 5.1 Introduction -- 5.2 Traumatic PNS Injury and Repair -- 5.3 Repair Phenotype of Schwann Cells -- 5.4 Remyelination -- 5.5 Conclusion -- References -- Chapter 6: Charcot-Marie-Tooth Disease -- 6.1 Introduction -- 6.2 Clinical Features of Charcot-Marie-Tooth Disease -- 6.3 Clinical Diagnosis -- 6.4 Genes Reported in CMT -- 6.5 Prevalence of CMT Diseases -- 6.6 Pathogenesis of CMT -- 6.6.1 PMP22 -- 6.6.1.1 Duplication -- 6.6.1.2 Point Mutation -- 6.6.2 P0/MPZ -- 6.6.3 SIMPLE -- 6.6.4 EGR2 -- 6.6.5 NEFL -- 6.6.6 Connexin 32 -- 6.6.7 GDAP1 -- 6.6.8 MTMR2 and MTMR13. , 6.6.9 SH3TC2/KIAA1985 -- 6.6.10 NDRG1 -- 6.6.11 PRX -- 6.6.12 Frabin/FGD4 -- 6.6.13 FIG4 -- 6.6.14 DNM2 -- 6.7 General Aspects of CMT Pathogenesis -- 6.7.1 UPR at ER -- 6.7.2 Ubiquitin-Proteasome Pathway -- 6.7.3 Aggresome-Autophagy Pathway -- 6.7.4 Inflammation -- 6.8 Therapeutic Approaches for CMT Diseases -- 6.8.1 Ascorbic Acid -- 6.8.2 Progesterone Antagonist -- 6.8.3 Neurotrophin-3 -- 6.8.4 RNA and Gene-Based Therapy -- 6.9 Conclusion -- References -- Chapter 7: Expression of the Transthyretin Gene in Schwann Cells and Familial Amyloidotic Polyneuropathy-Mediated Neurodegeneration -- 7.1 Introduction -- 7.2 The TTR Gene Is Expressed in the DRG -- 7.2.1 Reverse Transcription-Polymerase Chain Reaction Analysis of TTR in Human, Mouse, and Rat DRG -- 7.2.2 In Situ Hybridization Analysis of the TTR Gene in Mouse DRG -- 7.2.3 Laser Capture Microdissection Followed by RT-PCR to Increase Sensitivity for the Detection of TTR in Mouse DRG -- 7.2.4 Differences in Expression of the TTR Gene in the DRG of Humans and Rodents -- 7.3 Expression of the TTR Gene in Schwann Cells -- 7.3.1 Studies in the Peripheral Nerve -- 7.3.2 Further Confirmation of the Expression of the TTR Gene in Cultured Schwann Cells -- 7.3.3 Transgenic Mice Carrying the Human TTR Met30 Gene in a Mouse Ttr-Null Background -- 7.3.4 Physiological Role of TTR Synthesis in Schwann Cells and Satellite Cells -- 7.4 Pathogenesis of FAP -- 7.4.1 Neuropathology in FAP -- 7.4.2 Aggregation of TTR and Neurotoxicity -- 7.4.3 Liver Transplantation and Neuropathy -- 7.4.4 Schwann Cell Hypothesis -- 7.5 Conclusion -- References -- Chapter 8: Node of Ranvier Disruption: A Key Pathophysiology in Immune-Mediated Neuropathies -- Abbreviations -- 8.1 Introduction -- 8.2 Distinct Axonal Domains at and near Nodes of Ranvier -- 8.3 Acute Motor Axonal Neuropathy -- 8.4 Nodal Dysfunction/Disruption in AMAN. , 8.5 Possible Nodal Disruption by Various Anti-ganglioside Antibodies -- 8.6 Nodal Disruption Caused by Immune-Mediated Demyelination -- 8.7 Nodal and Paranodal Proteins as Autoimmune Targets -- 8.8 Conclusion -- References -- Chapter 9: Pathogenesis of Diabetic Neuropathy from the Point of View of Schwann Cell Abnormalities -- 9.1 Introduction -- 9.2 IMS32 Cells for the Study of Diabetic Neuropathy -- 9.3 Pathogenesis of Diabetic Neuropathy -- 9.3.1 Polyol Pathway Hyperactivity -- 9.3.2 Protein Kinase C Activity Abnormality -- 9.3.3 Oxidative Stress -- 9.3.4 Glycation -- 9.3.5 Impaired Neurotrophin Secretion -- 9.3.6 C-Peptide -- 9.4 Conclusion -- References -- Chapter 10: Spontaneously Immortalized Adult Rodent Schwann Cells as Valuable Tools for the Study of Peripheral Nerve Degeneration and Regeneration -- 10.1 Introduction -- 10.2 How to Establish Spontaneously Immortalized Schwann Cells? -- 10.2.1 Biological Basis for Schwann Cell Immortalization -- 10.2.2 Establishment of IMS32 Cells: Serum-Containing Culture with Fibroblast Elimination Using Anti-Thy-1.2 and Complement -- 10.2.3 Establishment of IFRS1 Cells: Serum-Free Culture Supplemented with NRG-β and Forskolin -- 10.3 Immortalized IMS32 Adult Mouse Schwann Cells -- 10.3.1 Biological Features of IMS32 Cells -- 10.3.2 IMS32 for the Study of Axonal Regeneration-Related Molecules -- 10.3.2.1 CNTF -- 10.3.2.2 Sonic Hedgehog (Shh) -- 10.3.2.3 GAL-1 -- 10.3.3 IMS32 Cells as a Valuable Tool for Studying Peripheral Neuropathy -- 10.3.3.1 Diabetic Neuropathy -- Polyol Pathway -- Glycation -- Oxidative Stress -- Reduced Synthesis of Neurotrophic Factors -- 10.3.3.2 Amyloid Polyneuropathy -- 10.4 Immortalized Schwann Cells from Murine Disease Models -- 10.4.1 Lysosomal Storage Diseases -- 10.4.1.1 NPC -- 10.4.1.2 Krabbe Disease (Twitcher) -- 10.4.1.3 Sandhoff Disease -- 10.4.1.4 Fabry Disease. , 10.4.2 CMT1B -- 10.4.3 Neurofibromatosis Type I (NF1) -- 10.5 Immortalized IFRS1 Adult Rat Schwann Cells -- 10.5.1 Biological Features of IFRS1 Cells -- 10.5.2 Myelination in Co-culture of IFRS1 Cells with Neurons -- 10.5.2.1 Adult Rat DRG Neurons -- 10.5.2.2 PC12 Cells -- 10.5.2.3 Motor Neurons -- 10.5.3 IFRS1 Cells for the Study of Axonal Degeneration and Regeneration -- 10.5.3.1 GAL-1 -- 10.5.3.2 Diabetic Neuropathy -- 10.6 Conclusion -- References -- Index.

Note: Intro -- Preface -- Contents -- Part I: Myelination in Neural Development and Regeneration -- 1: Cellular Signal-Regulated Schwann Cell Myelination and Remyelination -- 1.1 Introduction -- 1.1.1 Some Membrane Proteins and Lipids Are Composed of Myelin and Exist in Distinct Regions in Myelin -- 1.1.2 The Association Between Axon and Schwann Cells Regulate Myelination -- 1.1.3 Essential Role for Neuregulin-1 Type III in Schwann Cells Myelination and Remyelination -- 1.1.4 Small GTPases and Their Activator Are Essential for Schwann Cell Migration and Myelination -- 1.1.5 Intracellular Molecules Associated with Schwann Cell Myelination -- 1.1.6 Schwann Cell Myelination Is Required for Cytoskeleton Assembly and Disassembly -- 1.1.7 Cytoskeleton-Associated Proteins Regulate Schwann Cell Myelination -- 1.1.8 The Polarity Protein Par-3 and Its Binding Partners Regulate Schwann Cell Myelination -- 1.1.9 Activation of Arf6 Is Required for Schwann Cell Migration and Myelination -- 1.1.10 PI3K/Akt/mTOR Signal Pathway Is Necessary for Schwann Cell Myelination -- 1.1.11 Ga6-Tyro3 Signaling Pathway Is Included in Schwann Cell Myelination -- 1.1.12 Molecular Mechanisms of Pathogenesis in PNS Disorders -- 1.1.13 Prospective Clinical Treatment for Patients with PNS Disease -- References -- 2: Regulatory Mechanism of Peripheral Nerve Myelination by Glutamate-Induced Signaling -- 2.1 Introduction -- 2.2 ZNRF1 E3 Ubiquitin Ligase-Dependent Degradation of GS -- 2.3 Effect of Glutamate on Schwann Cells -- 2.4 Role of Glutamate Signaling on Peripheral Nerve Myelination -- 2.5 Role of Glutamate Signaling Regulation by ZNRF1 -- References -- 3: Cytoskeletal Signal-Regulated Oligodendrocyte Myelination and Remyelination -- 3.1 Introduction -- 3.2 Neural Cell Adhesion Molecule (NCAM) Signaling -- 3.3 Notch Signaling Pathways. , 3.4 Eph/Ephrin Signaling and β1 Integrin Pathways -- 3.5 Actin Cytoskeleton -- 3.6 Cadherin Super Family -- 3.7 Fyn Activation -- References -- 4: Activity-Dependent Myelination -- 4.1 Introduction -- 4.2 OPCs and Oligodendrocytes -- 4.3 Conclusions -- References -- 5: Heterogeneity of Oligodendrocytes and Their Precursor Cells -- 5.1 Introduction -- 5.2 Heterogeneity of Oligodendrocytes -- 5.2.1 Regional Differences of Oligodendrocytes in the CNS -- 5.2.2 Morphological Differences of Oligodendrocytes in the CNS -- 5.2.3 Selectivity of Axonal Sizes in Myelination by Oligodendrocytes -- 5.2.4 Oligodendrocyte Heterogeneity from Comprehensive Single-Cell RNA Sequencing -- 5.3 Heterogeneity of OPCs -- 5.3.1 OPCs from Distinct Regions in the CNS -- 5.3.2 OPCs in the Gray and White Matters -- 5.3.3 Region-Specific Differentiation of OPCs -- 5.4 Conclusion -- References -- Part II: Specialized Structures Along the Myelinated Nerve Fibers -- 6: Functional Domains in Myelinated Axons -- 6.1 Introduction -- 6.2 Structures and Protein Complexes at Specialized Axonal Domains -- 6.2.1 Axon Initial Segment and Nodes of Ranvier -- 6.2.2 Paranodes -- 6.2.3 Juxtaparanodes -- 6.3 Formation and Maintenance of Ion Channel Clustering at the Excitable Axonal Domains -- 6.3.1 Assembly of AIS -- 6.3.2 Formation and Maintenance of Nodes of Ranvier -- 6.4 Disruption of Paranodal Axoglial Junctions in Neurological Diseases -- 6.4.1 Mutant Mouse Models for Loss of the Paranodal Cell Adhesion Complex -- 6.4.2 Human Diseases Associated with Genetic Mutations of Paranodal Cell Adhesion Complex -- 6.4.3 Autoimmune Reactions Targeting the Paranodal Cell Adhesion Complex -- 6.4.4 Other Diseases Involving Paranodal Axoglial Junctions -- 6.5 Disruption of Axonal Domains Due to Breakdown of Nodal/Paranodal Proteins -- 6.6 Conclusion -- References. , 7: Physiology of Myelinated Nerve Conduction and Pathophysiology of Demyelination -- 7.1 Micro-anatomy of Myelinated Nerve Fibers -- 7.2 Resting Membrane Potential -- 7.3 Physiology of Axonal Ion Channels -- 7.4 Schwann Cell Ion Channels -- 7.5 Action Potential Propagation -- 7.6 Recording Methods -- 7.7 Experimental Demyelination -- 7.8 Repetitive Impulse Firing -- 7.9 Temperature-Dependent Block -- 7.10 Restoration of Conduction After Demyelination -- 7.11 Antibodies Against Gangliosides -- 7.12 Axonal Degeneration in Demyelinating Neuropathies -- References -- 8: Under the ECM Dome: The Physiological Role of the Perinodal Extracellular Matrix as an Ion Diffusion Barrier -- 8.1 The ECM in the Nervous System -- 8.1.1 The Molecular Composition of the ECM at the CNS Nodes -- 8.1.1.1 Link Proteins -- 8.1.1.2 Lecticans -- 8.1.1.3 Other ECMs -- 8.1.2 The Molecular Composition of ECM at the PNS Nodes -- 8.1.2.1 Gliomedin -- 8.1.2.2 Heparan Sulfate Proteoglycans -- 8.2 The ECM Complex in the Nervous System -- 8.2.1 The ECM Complex at the CNS Nodes -- 8.2.2 The ECM Complex at the PNS Nodes -- 8.3 The Functional Roles of the Perinodal ECM -- References -- 9: Oligodendrocyte Physiology Modulating Axonal Excitability and Nerve Conduction -- 9.1 Introduction -- 9.2 Modulation of Axonal Excitability -- 9.3 Modulation of Conduction Velocity -- 9.4 Magnitude of Oligodendrocyte Depolarization -- 9.5 Modulatory Effects Oligodendrocyte Depolarization on Axonal Conduction Revealed by Using Optogenetics -- 9.5.1 Advantage of the Use of the Mice Expressing Channelrhodopsin-2 in Oligodendrocytes -- 9.5.2 Facilitation of Axonal Conduction by Oligodendrocyte Depolarization -- 9.5.3 Early-Onset and Short-Lasting Facilitation of Axonal Conduction Induced by Oligodendrocyte Depolarization. , 9.5.4 Late-Onset and Long-Lasting Facilitation of Axonal Conduction Induced by Oligodendrocyte Depolarization -- 9.5.5 Oligodendrocyte Depolarization Facilitates Axonal Conduction in Different Brain Regions -- 9.5.6 Involvements of K+ Channels in the Facilitative Effects on Axonal Conduction -- 9.6 Suppressive Regulation of Axonal Conduction -- Possible Involvement of Adenosine A1 Receptors -- 9.7 Contribution of Perineuronal Oligodendrocytes to the Regulation of Axonal Activities -- 9.8 Concluding Remarks -- References -- 10: Mitochondrial Dynamics in Physiology and Pathology of Myelinated Axons -- 10.1 Introduction -- 10.2 General Behavior of Axonal Mitochondria -- 10.3 Mitochondrial Regulation in Myelinated Axons -- 10.4 Mitochondrial Alterations in Demyelinated Axons -- 10.5 Alterations of Axonal Mitochondria in Models of Congenital Myelin Disorders -- 10.6 Summary and Conclusions -- References -- 11: The Role of Sulfatides in Axon-Glia Interactions -- 11.1 Introduction -- 11.2 Glycosphingolipids in Cultured Oligodendrocytes -- 11.3 Role of Glycosphingolipids as Negative Regulators of Oligodendrocyte Differentiation in Culture and In Vivo -- 11.4 Roles of Glycosphingolipids in Myelin Morphology and Function In Vivo -- 11.5 Potential Mechanism of Sulfatide Function in Myelin -- 11.6 Importance of Paranodal Axo-Glial Junctions and/or Sulfatides in Axonal Homeostasis -- 11.7 Conclusion -- References -- 12: Structures and Molecular Composition of Schmidt-Lanterman Incisures -- 12.1 Schmidt-Lanterman incisure (SLI) -- 12.1.1 Structure of SLI -- 12.1.2 Shape Change of SLI During Nerve Stretch -- 12.1.3 Molecular Components in SLI -- 12.2 Membrane Skeletal Proteins in SLI -- 12.2.1 Protein 4.1G -- 12.2.2 MAGUK Family Proteins -- 12.2.2.1 MPP Family -- 12.2.2.2 Other MAGUKs -- 12.2.3 Intramembranous CADM Family -- 12.2.4 Lin7 Family Proteins. , 12.2.5 Myelin Abnormalities in 4.1G-/- Nerve Fibers in PNS -- 12.3 Overwork Weakness in Peripheral Neuropathy from Viewpoint of SLI -- 12.4 Conclusion -- References -- Part III: Myelin Pathology in the Central Nervous System -- 13: Pelizaeus-Merzbacher Disease: Molecular and Cellular Pathologies and Associated Phenotypes -- 13.1 Leukodystrophies -- 13.2 Phenotypes Resulting from CNS Hypomyelination Due to Dysfunctional Myelin Development -- 13.2.1 Hypomyelinating Leukodystrophies -- 13.2.2 PMD, a Hypomyelinating Leukodystrophy -- 13.2.3 Discovery of PLP1 Mutations in Patients with PMD -- 13.2.4 Genotype-Phenotype Correlations in PMD and Related Disorders -- 13.3 Distinct Molecular Mechanisms Underlying Different PLP1 Mutations Associated with PMD -- 13.3.1 Cellular Pathology of Point Mutations Resulting in Amino Acid Substitutions -- 13.3.2 Genomic and Cellular Pathology Underlying PLP1 Duplications -- 13.3.3 PLP1 Null Mutations -- 13.3.4 Hypomyelination of Early Myelinating Structures: An Alternative Phenotype of PLP1 Mutations -- 13.4 Conclusions -- References -- 14: Multiple Sclerosis -- 14.1 Introduction -- 14.2 Basic Aspects -- 14.2.1 Epidemiology -- 14.2.2 Environmental Aspects -- 14.2.3 Genetic Aspects -- 14.2.4 Pathology -- 14.2.4.1 White Matter Involvement -- 14.2.4.2 Gray Matter Involvement -- 14.2.4.3 Glial Inflammation -- 14.2.5 Pathogenesis: Immune Mechanism of MS -- 14.3 Clinical Aspects -- 14.3.1 Clinical Course -- 14.3.2 Clinical Symptoms and Signs -- 14.3.3 Laboratory Findings -- 14.3.3.1 Magnetic Resonance Imaging Findings -- 14.3.3.2 Other Laboratory Findings -- 14.4 Diagnosis -- 14.5 Prognosis -- 14.6 Treatment -- 14.6.1 Treatment of Acute Relapse -- 14.6.2 Prevention of Relapse and Disability Progression -- 14.6.2.1 DMTs for RRMS -- 14.6.2.2 DMTs for Progressive MS -- 14.6.3 Symptomatic Therapy -- References. , 15: Visualization of Myelin for the Diagnosis and Treatment Monitoring of Multiple Sclerosis.