Handbook of Neurochemistry and Molecular Neurobiology: Development and Aging Changes in the Nervous System

Cover......Page 1
Handbook of Neurochemistry and Molecular Neurobiology: Development and Aging Changes in the Nervous System......Page 2
Copyright......Page 4
Preface......Page 5
Contributors......Page 6
Table of Contents......Page 8
Neurotrophins and Central Nervous System Development......Page 10
1 Introduction......Page 11
2 Neurotrophins and CNS Neuronal Survival......Page 12
2.1 NGF and the Survival of Central Cholinergic Neurons......Page 13
2.2.2 Mesencephalic Trigeminal Nucleus Neurons......Page 14
2.2.3 Neurons of Other Regions of the Brain......Page 15
3.1.1 Radial Migration......Page 16
3.2 Modulation of Neuronal Migration in the Cerebellum by BDNF and NT-3......Page 18
4 Neurotrophins and CNS Dendritic Development......Page 19
4.2 Effects of Exogenous Neurotrophins on the Dendrites of Non-Pyramidal Interneurons and Other Neuronal Types......Page 20
4.3 Role of Endogenous Neurotrophins in Dendritic Differentiation......Page 21
4.4 Neurotrophin Receptors and Downstream Signaling Pathways Involved in Dendritic Development......Page 22
References......Page 23
Nerve Growth Factor Regulated Gene Expression......Page 30
2 The Role of Regulated Gene Expression in the NGF Mechanism-What Genes Does NGF Regulate and Why Do We Want to Know?......Page 31
4 Long-Term Regulation of Gene Expression by NGF-Results of a SAGE Study with PC12 Cells......Page 32
5 Closing Remarks......Page 61
References......Page 62
Myelinating Cells in the Central Nervous System-Development, Aging, and Disease......Page 70
1.1 General Developmental Stages/Scheme......Page 71
1.2.2 Dorsal Spinal Cord Development......Page 73
1.2.3 Glial-Restricted Precursor Cell Hypothesis......Page 75
1.4 Oligodendrocyte Development from the SVZ......Page 76
1.5 Myelination......Page 78
2 Axon-Myelin Membrane......Page 79
3 Aging and Alzheimer\'s Disease......Page 80
References......Page 83
Sulfur-Containing Amino Acids in the CNS: Homocysteine......Page 86
2 Overview of Methionine Metabolism in the CNS......Page 87
3 Homocysteine and Metabolic Diseases......Page 89
4 Homocysteine as a CNS Risk Factor......Page 90
5 Homocysteine: Potential Mechanisms of Action......Page 91
6 Methodological Issues......Page 93
References......Page 94
Stress Response Signal Transduction......Page 98
2 Homeostasis: Stress, Inflammation, and Recovery......Page 99
4 Cytokine Responses and Cell Survival......Page 100
5 Transcription Factors: NF-kappaB......Page 101
6 Inflammatory Gene Expression: COX-2 and iNOS......Page 104
8 Conclusion......Page 105
References......Page 106
Aging and Oxidative Stress Response in the CNS......Page 112
1 Introduction......Page 113
2 The Free-Radical Hypothesis of Aging......Page 114
2.1 The Mitochondrial Theory of Aging......Page 117
3.1 Neurogasobiology of Nitric Oxide and Carbon Monoxide: Two Molecules That Promote Adaptive Responses in the CNS......Page 119
3.3 Nitric Oxide as a Neurotransmitter......Page 120
3.5 Regulation of Gene Expression by Oxidative and Nitrosative Stress......Page 121
3.6 Carbon Monoxide: A Signaling Molecule Endowed with Antiinflammatory Properties......Page 122
3.7 The Heat-Shock Pathway of Brain Stress Tolerance......Page 124
3.8 HO System: A Putative Vitagene Target for Neuroprotection......Page 126
3.9 Regulation of HO Genes......Page 127
3.10 Glutathione, Thiol Redox State, and RNS: Intracellular Modulators of HO-1 Expression......Page 128
3.11 Heme Oxygenase in Brain Function and Dysfunction......Page 129
3.12 Bilirubin and Biliverdin: An Endogenous Antioxidant System......Page 130
4 Caloric Restriction and Endogenous Oxidative Stress: Relevance to Aging and Cell Survival......Page 131
5 Major CNS Disorders Associated with ROS/RNS-Mediated Damage......Page 132
5.1 Amyotrophic Lateral Sclerosis......Page 133
5.2 Alzheimer\'s Disease......Page 134
5.3 Parkinson\'s Disease......Page 135
5.4 Multiple Sclerosis......Page 137
5.5 Friedreich\'s Ataxia......Page 139
5.7 Down\'s Syndrome......Page 141
6 Genetics of Human Longevity: Role of Vitagenes in Prolongation of Healthy Life Span......Page 142
7 HO-1 and Hsp70 as a Therapeutic Funnel......Page 143
8 Conclusion......Page 145
References......Page 146
Parallels Between Neurodevelopment and Neurodegeneration: A Case Study of Alzheimer\'s Disease......Page 156
2.1.1 Amyloid-beta Protein Precursor......Page 157
3.1 Cell-Cycle Control......Page 158
3.4 An Early, Not a Late, Change......Page 159
4.3 Gender Differences and Hormones......Page 160
5 Conclusions......Page 161
References......Page 162
Differentiation and De-Differentiation-Neuronal Cell-Cycle Regulation During Development and Age-Related Neurodegenerative Disorders......Page 166
1.1 Cyclin-Dependent Kinases-Key Regulators of the Cell Cycle......Page 169
1.2.1 Cyclins......Page 170
1.2.2 Protein Phosphorylation......Page 173
1.2.4 Subcellular Sorting and Degradation of Cell-Cycle Regulating Proteins......Page 174
1.3 Effects of Cdk Activation-Cdk Substrates-The Retinoblastoma Protein......Page 175
1.4 Quality Control of Cell-Cycle Progression by \"Stop\" and \"Go\" Signals: Restriction Point and  Checkpoints......Page 176
1.5.1 Growth Factor Signaling-The Ras-MAPK Pathway......Page 177
1.5.3 Convergence of Ras and Integrin-Dependent Signaling......Page 179
2.1 Stem Cell Proliferation and Neurogenesis......Page 181
2.3.1 Apoptosis......Page 183
2.3.2 The Bcl-2 Family......Page 187
2.3.4 Nitric Oxide......Page 188
2.3.5.4 NF-kappaB......Page 189
3 Cell-Cycle Regulators in Neurodegeneration......Page 190
3.1.2 Potential Risks of Dynamic Stabilization of Neuronal Connectivity......Page 191
3.1.3 Aberrant Plasticity in AD......Page 193
3.2.1.2 MAPK......Page 194
3.2.2 Oxidative Stress and the Autocrine Loop of Self-Perpetuating Mitogenic Activation......Page 195
3.2.3 The Replay of Developmental Programs in Alzheimer\'s Disease......Page 198
3.2.4.2 Cyclins......Page 199
3.2.4.3 Cdk Inhibitors......Page 200
3.2.4.5 The Cell Cycle Integrates Intercellular and Intracellular Signaling and Links Development, Oncogenesis, and Neurodegen......Page 201
References......Page 205
mRNA Modulations in Stress and Aging......Page 224
1.1 Defining Stress......Page 225
1.2 The HPA Axis: Neuroendocrine Response to Stress......Page 226
1.4 Other Stress-Related Hormones......Page 227
1.5 Stress and the Brain......Page 228
2.1 The Splicing Machinery......Page 229
2.2 SR Proteins......Page 230
3.1 Constitutive Splicing......Page 231
3.2 Alternative Splicing......Page 232
3.3 Stress-Induced Changes in SR-Related Proteins......Page 233
5 Defects in pre-mRNA Splicing as Causes of and Predisposition to Diseases......Page 234
6.1 Pre-mRNA Splicing Modulations in Senescence......Page 236
7 Candidate Gene Study: ACHE......Page 239
7.1 The Molecular Biology of AChE......Page 240
7.2 AChE in Multitissue Stress Responses......Page 241
8 AChE\'s 3\' Alternative Splicing under Stress: Long-Term Implications......Page 242
9 Conclusions......Page 244
References......Page 245
Molecular Mechanisms of Dendritic Spine Plasticity in Development and Aging......Page 254
2 The Structure of Dendritic Spine Synapses......Page 255
3 The Postsynaptic Density of the Spinous Synapse......Page 256
4 Synaptogenesis and the Formation of Dendritic Spine Synapses......Page 259
5 Molecular Dynamics of the Plastic Spine or What are Spines Good for......Page 260
6 Molecular Mechanisms of Spine Plasticity......Page 262
8 The Dendritic Spine in the Aging Brain......Page 263
References......Page 265
Alzheimer\'s Disease BACE Proteases......Page 270
1 Introduction to Alzheimer\'s Disease......Page 271
2 The Discovery of BACE Proteases......Page 273
3 BACE Gene Structure and Alternative Splicing......Page 274
4 Transcription and Translation of BACE1......Page 277
5.1 Posttranslational Modifications and Intracellular Transport......Page 280
5.2 BACE1 Interacting Proteins......Page 281
6.4 BACE1 Expression in AD......Page 283
6.5 Astrocytic BACE1 Expression......Page 284
7.1 Substrates of BACE Proteases......Page 285
References......Page 287
Protein Misfolding, a Common Mechanism in the Pathogenesis of Neurodegenerative Diseases......Page 294
1 Introduction......Page 295
2 Role of Protein Misfolding and Aggregation in Disease......Page 296
3.1 Alzheimer\'s Disease......Page 297
3.3 Huntington Disease......Page 299
3.4 Amyotrophic Lateral Sclerosis......Page 300
3.5 Prion Diseases......Page 301
4 Animal Models of Neurodegenerative Diseases......Page 302
5 Structural and Mechanistic Basis of Protein Misfolding and Aggregation......Page 303
7 Targets for Therapy......Page 305
References......Page 307
Anti-Aging Strategies......Page 314
1 Introduction......Page 315
2 Muscarinic Receptors and Aging......Page 316
3 Muscarinic Receptors and Oxidative Stress......Page 317
4 Consequences of Aging on Cholinergic Function......Page 318
5 The Effects of Fruit and Vegetable Supplementation on Behavioral and Neuronal Deficits in Aging......Page 319
References......Page 321
Index......Page 328