Note: Intro -- Preface -- Contents -- Contributors -- Chapter 1: Introduction to the Complexity of Cell Surface and Tissue Matrix Glycoconjugates -- 1.1 Introduction -- 1.2 Monosaccharides: Building Blocks of Glycans -- 1.3 Formation of Oligosaccharides -- 1.4 Classification of Glycans -- 1.5 Structural Features of  N -Glycans -- 1.6 Structural Features of  O -Glycans -- 1.7 Biosynthesis of  N - and  O -Glycans -- 1.8 Glycosphingolipids -- 1.9 Structural Features of the Glycan Moieties of Glycosphingolipids -- 1.10 Synthesis and Functions of the Glycan Moieties of Glycolipids -- 1.11 Glycosylphosphatidylinositol Anchors: A Special Group of Glycolipids -- 1.12 Glycosaminoglycans and Proteoglycans -- 1.13 Glycans of Cell Surface Glycoconjugates Perform a Variety of Functions -- 1.14 Summary -- References -- Chapter 2: Introduction to Cells Comprising the Nervous System -- 2.1 Introduction -- 2.2 Neurons -- 2.2.1 Dendrites -- 2.2.2 Axon -- 2.3 Glia -- 2.3.1 Astrocytes -- 2.3.2 Oligodendrocytes and Myelin -- 2.3.3 Microglia -- 2.4 Summary -- References -- Chapter 3: Synthesis, Processing, and Function of N-glycans in N-glycoproteins -- 3.1 Introduction -- 3.2 N-Glycans Are First Born on a Lipid and then Transferred "En Bloc" onto the Nascent N-Glycoprotein in the ER -- 3.3 Trimming, Reglycosylation, and Remodeling: There Are Many Ways of N-Glycoprotein Processing in the ER and Golgi -- 3.4 The Essential Toolbox of a Glycobiologist: A Brief History of the Discovery of N-Glycoprotein Biosynthesis Inhibitors and Their Impact on Our Understanding of N-Glycan Processing -- 3.5 Sweet Encounters of Proteins and Lipids: N-Glycans Affect the Subcellular Distribution and Complex Formation of Enzymes in Glycolipid Biosynthesis -- 3.6 Conclusions and Epilogue: The Tale of the Tail That Wags the Dog -- References. , Chapter 4: Synthesis of O-Linked Glycoconjugates in the Nervous System -- 4.1 Introduction -- 4.2 Biosynthesis of O-Linked Proteins -- 4.2.1 O-GalNAcylation -- 4.2.2 O - Mannosylation -- 4.2.3 O-GlcNAcylation -- 4.2.4 O-Xylosylation -- Heparan Sulfate -- Chondroitin Sulfate -- 4.2.5 O-Fucosylation -- 4.2.6 O-Glucosylation -- 4.3 Biosynthesis of O-Linked Lipids -- 4.3.1 Glucosylceramide and Glycosphingolipids -- 4.3.2 Galactosylceramide and Glycosphingolipids -- 4.3.3 Other O-Linked lipids -- Cholesterylglucoside -- Phosphatidylglucoside -- 4.4 Conclusions -- References -- Chapter 5: Chemistry and Function of Glycosaminoglycans in the Nervous System -- 5.1 Introduction -- 5.2 Glycosaminoglycan Structure and Chemistry -- 5.2.1 Chondroitin Sulfate -- Structure and Chemistry -- Synthesis and Modification of CS Chains -- CS Proteoglycans in Brain -- 5.2.2 Dermatan Sulfate -- 5.2.3 Heparin -- 5.2.4 Heparan Sulfate -- Structure and Chemistry -- Synthesis and Modification of HS Chains -- HS Proteoglycans in Brain -- 5.2.5 Keratan Sulfate -- 5.2.6 Hyaluronan -- 5.3 Function of GAGs in the Brain -- 5.3.1 GAG Interactions and Binding Partners -- 5.3.2 GAG Functions -- Neural System Development -- Brain Patterning -- Neurite Outgrowth and Migration -- Differentiation and Stem-Cell Niche -- Synaptic Plasticity -- 5.3.3 Injury Response -- 5.3.4 GAGs and Human Neural Diseases -- 5.4 Concluding Remarks -- References -- Chapter 6: Use of Glycan-Targeted Antibodies/Lectins to Study the Expression/Function of Glycosyltransferases in the Nervous System -- 6.1 Introduction -- 6.2 HNK-1 Epitope -- 6.3 O-Mannose Glycans in the Brain -- 6.4 GnT-IX Is a Brain-Specific O-Mannose Branching Enzyme -- 6.5 In Vivo Enzymatic Functions of GnT-IX and GnT-V -- 6.6 GnT-IX-Deficient Mice Show Enhanced Recovery from Demyelinating Damage -- References. , Chapter 7: From Mass Spectrometry-Based Glycosylation Analysis to Glycomics and Glycoproteomics -- 7.1 Overview and Scope -- 7.2 Mass Spectrometry for Glycosylation Analysis -- 7.2.1 A Primer for MALDI-MS and LC-ESI-MS -- 7.2.2 LC Separation -- 7.2.3 Chemical Derivatization -- 7.2.4 MS/MS Sequencing -- 7.2.5 Summary and Perspectives -- 7.3 Increasing the Breadth and Depth of MS-Based Glycomic Coverage -- 7.3.1 Addressing Poly- N -acetyllactosaminoglycans -- 7.3.2 Addressing Terminal Disialyl Motif and Polysialylation -- 7.3.3 Addressing Sulfoglycomics -- 7.3.4 Summary and Perspectives -- 7.4 From Glycomics to Glycobiology-Driven Glycoproteomics -- 7.4.1 Raison d'etre and the Inadequacy of Only Defining Site Occupancy -- 7.4.2 MS/MS Sequencing and Identification of Glycopeptides -- 7.5 Closing and Future Prospects -- References -- Chapter 8: Structural Analysis of Oligosaccharides and Glycoconjugates Using NMR -- 8.1 Introduction -- 8.2 Basic NMR Phenomena -- 8.3 Chemical Shifts as Structural Probes -- 8.4 Through "BOND" and Through "SPACE" Interactions -- 8.5 Relaxation and Molecular Motion -- 8.6 Paramagnetic Effects as Sources of Long-Distance Information -- 8.7 Chemical Exchange: Dynamic Aspects in NMR -- 8.8 NMR Tools for Intermolecular Interaction Analysis -- 8.8.1 Oligosaccharide-Protein Interactions -- 8.8.2 Protein Binding to Glycolipid Clusters -- 8.9 Liaisons Between NMR and Computation -- References -- Chapter 9: Glycolipid and Glycoprotein Expression During Neural Development -- 9.1 Introduction -- 9.2 Glycobiology During Early Embryogenesis -- 9.3 Neural Tube Formation -- 9.4 Neuroepithelial Cells and Radial Glial Cells -- 9.4.1 Neural Stem Cells in Development -- Notch -- 9.4.2 Neuroepithelial Cells, Radial Glial Cells, and Intermediate Progenitor Cells -- NECs -- RGCs -- IPCs -- SSEA-1 -- Prominin-1 -- Gangliosides. , Heparin Sulfate Proteoglycans and Chondroitin Sulfate Proteoglycans -- 9.5 Neurogenesis -- 9.5.1 Polysialic Acid-Neural Cell Adhesion Molecule -- 9.5.2 9-O-Acetyl GD3 -- 9.5.3 Gangliosides -- 9.6 Gliogenesis -- 9.6.1 Oligodendrogenesis -- A2B5 -- NG2 -- O4 and O1 -- 9.6.2 Astrogliogenesis -- gp130 -- PtdGlc -- Gangliosides -- 9.7 Adult NSCs and Niche -- 9.7.1 SVZ -- 9.7.2 SGZ -- 9.7.3 Glycoconjugates in Adult NSCs -- 9.7.4 Lectins -- 9.8 Neural Crest Cells -- 9.8.1 HNK-1 -- 9.8.2 PSA-NCAM -- 9.8.3 Other Glycoconjugates -- 9.9 Future Studies -- References -- Chapter 10: Gangliosides and Cell Surface Ganglioside Glycohydrolases in the Nervous System -- 10.1 Gangliosides -- 10.2 Gangliosides and Membrane Organization -- 10.3 Metabolic Pathways of Gangliosides -- 10.4 Plasma Membrane-Associated Enzymes and Ganglioside Pattern -- 10.5 Plasma Membrane Glycosphingolipid Hydrolases in the Nervous System -- 10.5.1 Sialidase Neu3 -- 10.5.2 β-Glucocerebrosidases -- 10.5.3 β-Galactosidases -- 10.5.4 β-Hexosaminidases -- 10.6 Conclusions -- References -- Chapter 11: Role of Myelin-Associated Glycoprotein (Siglec-4a) in the Nervous System -- 11.1 Introduction -- 11.2 MAG Structure and Expression -- 11.3 Role of MAG in Axon-Myelin Interaction/Stability -- 11.4 MAG as an Inhibitor of Axon Regeneration -- 11.5 Nurturing/Protective Properties of MAG on Neurons -- 11.6 MAG as a Functional Receptor in Oligodendrocytes -- 11.7 Future Perspectives -- References -- Chapter 12: Role of Galactosylceramide and Sulfatide in Oligodendrocytes and CNS Myelin: Formation of a Glycosynapse -- 12.1 Requirement for Myelin Glycosphingolipids for Maintenance of the Myelin Sheath -- 12.2 Functions of Myelin Glycosphingolipids -- 12.3 Involvement of OLG/Myelin GSLS in Signaling -- 12.4 Natural Ligands That Interact with GalC and SGC and Transmit Signals Across Apposed Membranes. , 12.5 Binding and Effect of Multivalent Glyco-nanoparticles on OLGS -- 12.6 Receptors in OLGS Which Interact with Multivalent Gal/SGal by Trans Interactions -- 12.7 GalC/SGC Signaling Releases Cytoskeletal Restriction of Membrane Domains -- 12.8 Role of MBP in Transmission of GalC/SGC-Mediated Signal -- 12.9 Role of Glycosynapses in OLGS or Myelin -- 12.10 Treatment of Demyelinating Disease by Stimulation of OLGS by GSL Cross-Linking -- References -- Chapter 13: Glycosignaling: A General Review -- 13.1 Introduction: Definition of "Glycosignaling" -- 13.2 Isolation of Glycosignaling Complexes from Brain -- 13.3 Glycosignaling, Biosynthesis, and Brain Development -- 13.4 The Glycocalyx as a Barrier to Glycosignaling -- 13.5 Glycosignaling Heterogeneity in Specific Brain Regions -- 13.6 Evidence That Fatty Acids and Sphingosine Base Heterogeneity Can Affect Glycosignaling: Toxins -- 13.7 Glycosignaling, Rho-GTPase, and Axonal Growth -- 13.8 Glycosignaling and Protein Phosphorylation -- 13.9 Lysosomal Storage Modifies Glycosignaling -- 13.10 Future Directions for Glycosignaling in the Brain -- References -- Chapter 14: Glycosphingolipids in the Regulation of the Nervous System -- 14.1 Introduction -- 14.2 Glycosphingolipids in Cultured Cells -- 14.2.1 Gangliosides Modulate Signals Transduced by Neurotrophic Factors/Receptors -- 14.2.2 Essential Roles of GSLs for Development of Multicellular Organisms -- 14.3 Impact of KO of Glycosyltransferase Genes Located at Stem Steps of GSL Synthesis -- 14.3.1 KO of ST3GAL5 (GM3 Synthase) in Mice -- 14.3.2 KO of UGT8 (GalCer Synthase) and GAL3ST1 (Sulfatide Synthase) in Mice -- 14.3.3 LacCer Synthase KO Mice -- 14.4 Compensation for Lost Functions by Remaining GSLS -- 14.5 Double KO Exhibited More Severe Phenotypes -- 14.6 Response to Neurodegeneration by Modification of Gene Expression in the DKO mice. , 14.7 Mechanisms by Which Gangliosides May Maintain the Integrity of the CNS.

Note: Intro -- Preface -- Postscript: In Memoriam -- Contents -- Chapter 1: Introduction to the Complexity of Cell Surface and Tissue Matrix Glycoconjugates -- 1 Introduction -- 2 Monosaccharides: Building Blocks of Glycans -- 3 Formation of Oligosaccharides -- 4 Classification of Glycans -- 5 Structural Features of N-Glycans -- 6 Structural Features of O-Glycans -- 7 Biosynthesis of N- and O-Glycans -- 8 Glycosphingolipids -- 9 Structural Features of the Glycan Moieties of Glycosphingolipids -- 10 Synthesis and Functions of the Glycan Moieties of Glycolipids -- 11 Glycosylphosphatidylinositol Anchors: A Special Group of Glycolipids -- 12 Glycosaminoglycans and Proteoglycans -- 13 Glycan-Protein Interactions -- 14 Glycans of Cell Surface Glycoconjugates Perform a Variety of Functions -- 15 Summary -- References -- Chapter 2: Cells of the Central Nervous System: An Overview of Their Structure and Function -- 1 Introduction -- 2 Neurons -- 2.1 Neuronal Cell Body -- 2.2 Cytoskeleton -- 2.3 Dendrites -- 2.4 Axon -- 2.5 Synapse -- 3 Supporting Cells -- 3.1 Astrocytes -- 3.2 Oligodendrocytes -- 3.3 Microglia -- 3.4 NG2 Cells (Polydendrocytes) -- 3.5 Ependymal Cells -- 4 Extracellular Matrix -- 5 Concluding Remarks -- References -- Chapter 3: Synthesis, Processing, and Function of N-Glycans in N-Glycoproteins -- 1 Introduction -- 2 N-glycans Are First Born on a Lipid and Then Transferred "En Bloc" onto the Nascent N-glycoprotein in the ER -- 3 Trimming, Reglycosylation, and Remodeling: There Are Many Ways of N-glycoprotein Processing in the ER and Golgi -- 4 The Essential Toolbox of a Glycobiologist: A Brief History of the Discovery of N-glycoprotein Biosynthesis Inhibitors and Their Impact on Our Understanding of N-glycan Processing. , 5 Sweetening the Bond or Sugar-Coating Bad News: Recent Advances in the Role of N-glycans for Virus Infections and Immune Responses -- 6 Sweet Encounters of Glycoproteins and Glycolipids: N-glycans Affect the Subcellular Distribution and Complex Formation of Enzymes in Glycolipid Biosynthesis -- 7 Conclusions and Epilogue: The Tale of the Tail That Wags the Dog -- References -- Chapter 4: Synthesis of O-Linked Glycoconjugates in the Nervous System -- 1 Introduction -- 2 Biosynthesis of O-Linked Proteins -- 2.1 O-GalNAcylation -- 2.2 O-Mannosylation -- 2.3 O-GlcNAcylation -- 2.4 O-Xylosylation -- 2.5 O-Fucosylation -- 2.6 O-Glucosylation -- 3 Biosynthesis of O-Linked Lipids -- 3.1 Glucosylceramide and Glycosphingolipids -- 3.2 Galactosylceramide and Glycosphingolipids -- 3.3 GlcCer and GM3 Synthase Deficiency in Human and Mouse -- 3.4 Other O-Linked Lipids - New Glucose-Related Lipids -- 4 Conclusions -- References -- Chapter 5: Chemistry and Function of Glycosaminoglycans in the Nervous System -- 1 Introduction -- 2 Glycosaminoglycan Structure and Chemistry -- 2.1 Chondroitin Sulfate (CS) -- 2.1.1 Structure and Chemistry -- 2.1.2 Synthesis and Modification of CS Chains -- 2.1.3 CS Proteoglycans (CSPGs) in Brain -- 2.2 Dermatan Sulfate (DS) -- 2.3 Heparin -- 2.4 Heparan Sulfate (HS) -- 2.4.1 Structure and Chemistry -- 2.4.2 Synthesis and Modification of HS Chains -- 2.4.3 Heparan Sulfate Proteoglycans (HSPGs) in Brain -- 2.5 Keratan Sulfate (KS) -- 2.6 Hyaluronan (HA) -- 3 Function of GAGs in the Brain -- 3.1 GAG Interactions and Binding Partners -- 3.2 GAG Functions During Brain Development -- 3.2.1 Neural System Development and Lineage Specification -- 3.2.2 Brain Patterning -- 3.2.3 Neurite Outgrowth, Axonal Pathfinding and Migration -- 3.2.4 Differentiation and Stem-Cell Niche -- 3.2.5 Synaptic Plasticity. , 3.3 GAG Function in CNS-Associated Disorders and Injury -- 3.3.1 Injury Response -- 3.3.2 Neurological Disorders -- 3.3.3 Inflammation -- 3.3.4 Tumorigenesis -- 4 Concluding Remarks -- References -- Chapter 6: Structural Analysis of Oligosaccharides and Glycoconjugates Using NMR -- 1 Introduction -- 2 Basic NMR Phenomena -- 3 Chemical Shifts as Structural Probes -- 4 Through "BOND" and Through "SPACE" Interactions -- 5 Relaxation and Molecular Motion -- 6 Paramagnetic Effects as Sources of Long-Distance Information -- 7 Chemical Exchange: Dynamic Aspects in NMR -- 8 NMR Tools for Intermolecular Interaction Analysis -- 8.1 Oligosaccharide-Protein Interactions -- 8.2 Protein Binding to Glycolipid Clusters -- 9 Liaisons Between NMR and Computation -- References -- Chapter 7: Glycans and Carbohydrate-Binding/Transforming Proteins in Axon Physiology -- 1 Introduction -- 2 Axon Determination/Early Neuronal Differentiation -- 3 Axon Guidance -- 3.1 Axon Guidance by Glycosylated Cell Adhesion Molecules (CAMs) -- 3.2 Glycosaminoglycans in Axon Guidance -- 3.3 Galectins and Their Interactions with Guidance Cues in the Adult Olfactory System -- 4 Axon/Glia Interactions -- 5 Nerve Impulse Generation/Transmission -- 5.1 Voltage-Gated Ion Channels -- 5.2 Voltage-Gated Sodium Channels -- 5.3 Voltage-Gated Potassium Channels -- 5.4 Voltage-Gated Calcium Channels -- 5.5 O-Linked β-N-Acetylglucosaminylation of AIS Proteins -- 6 Axon Regeneration -- 7 New Perspective in CNS Regulation Through Glycan-Lectin Interactions in the Microbiota-Gut-Brain Axis -- References -- Chapter 8: Neurological Consequences of Congenital Disorders of Glycosylation -- 1 Introduction -- 2 Classification -- 2.1 N-Linked Glycosylation Defects -- 2.2 O-Linked Glycosylation Defects -- 2.3 Disorders of Glycosylphosphatidylinositol (GPI) Anchor Biosynthesis. , 2.4 Disorders of Glycosphingolipid (GSL) Glycosylation -- 2.5 Disorders of Multiple Glycosylation Pathways -- 2.6 Recently Described CDG with Neurological Presentation -- 3 Markers/Biochemical Abnormalities -- 4 Congenital Brain Abnormalities -- 5 Epilepsy -- 6 Developmental Delay/Intellectual Disability -- 7 Ataxia -- 8 Neuromuscular Presentation -- 9 Spasticity -- 10 Autistic Features -- 11 Extrapyramidal Manifestation -- 12 Treatment Options -- 13 Conclusions and New Perspectives -- References -- Chapter 9: Brain O-GlcNAcylation: From Molecular Mechanisms to Clinical Phenotype -- 1 Introduction -- 2 O-GlcNAc Is a Ubiquitous Monosaccharide That Cycles Onto and Off Serine and Threonine -- 2.1 O-GlcNAc Is Not Elongated to Yield Complex Oligosaccharides -- 2.2 O-GlcNAc Is Mostly Expressed on the Inside of Cells in Multicellular Organisms -- 2.3 O-GlcNAc Can Be Dynamically Attached and Removed -- 3 O-GlcNAc Is Added to Proteins by OGT and Removed by OGA -- 3.1 Only Two Enzymes Regulate the Cycling of O-GlcNAc -- 3.2 O-GlcNAc Transferase -- a Highly Conserved Glycosyltransferase Present in the Nucleus & -- Cytosol -- 3.3 O-GlcNAcase -- a Cytosolic O-β-GlcNAc Hydrolase with Neutral pH Optima -- 4 O-GlcNAc Is Highly Expressed in the Nervous System -- 4.1 O-GlcNAc Is Found Throughout the Brain -- 4.2 Thousands of Neuronal Proteins Are Modified by O-GlcNAc -- 4.3 O-GlcNAc Regulates Diverse Cellular Processes -- 5 O-GlcNAc Is Essential for Brain Function -- 5.1 Early and Late Brain Development Depends Upon O-GlcNAc Cycling -- 5.2 O-GlcNAc Underlies Learning and Memory -- 5.3 Impaired O-GlcNAc Cycling Contributes to Neurodegenerative Disease -- 5.4 O-GlcNAc Mediates Central Control of Metabolism -- 6 Summary and Outlook -- References -- Chapter 10: Ganglioside Microdomains on Cellular and Intracellular Membranes Regulate Neuronal Cell Fate Determination. , 1 Introduction -- 2 Ganglioside Multifunction in Cell Membranes and Intracellular Organelles -- 3 Ganglioside microdomains for Neuronal Cell Fate Determination -- 4 GD3-EGFR -- 5 GD3 Regulates Mitochondrial Dynamics by Interacting with Drp1 -- 6 GD3 Amplifies SOX2 Expression and GM1 Promotes DCX Expression -- 7 GM1 Binds to Neuronal Gene Promoter Regions -- 8 Nuclear GM1 Promotes Neuronal Gene Expression -- 9 Other Gangliosides for NSC Specification -- 10 Future Studies -- References -- Chapter 11: Gangliosides and Cell Surface Ganglioside Metabolic Enzymes in the Nervous System -- 1 Gangliosides -- 1.1 Ceramide: The Lipid Portion of Gangliosides -- 1.2 The Oligosaccharide Portion of Gangliosides -- 2 Gangliosides and Membrane Organization -- 3 Metabolic Pathways of Gangliosides -- 4 Plasma Membrane-Associated Enzymes and Ganglioside Pattern -- 5 Sialidases, Sialyltransferases and Plasma Membrane Sialidase Neu3 -- 6 β-Hexosaminidase and N-Acetylgalactosaminyltransferase -- 7 β-Glucocerebrosidase -- 8 β-Galactosidase -- 9 Membrane Dynamics: A Non-canonical Pathway Involved in the Establishment of the GSL Profile at the Plasma Membrane -- 10 Conclusions -- References -- Chapter 12: Neuronal Ganglioside and Glycosphingolipid (GSL) Metabolism and Disease -- 1 Historical Aspects of Structure, Location and Function of GSLs -- 2 Significance and Function of Neuronal GGs -- 3 Intracellular Pathways of GG and GSL Metabolism -- 4 Emerging Concepts of GSL & -- GG Metabolism at Organellar Membranes -- 5 Emerging Topology of Glycolipid Biosynthesis -- 6 Generation of Cell-Type-Specific Ganglioside Patterns -- 7 Enzyme Catalysis at Membrane Surfaces -- 8 GSL Biosynthesis and Salvage Pathways -- 8.1 Ceramide Synthesis -- 8.2 Ganglioside Synthesis and Function -- 9 Inherited Errors of GG Biosynthesis -- 10 Remodeling and Recycling of Cell Surface Gangliosides. , 11 Concepts of the Constitutive Degradation of Gangliosides and Glycosphingolipids at ILVs.