Oxidative Stress and Neurodegenerative Disorders (eBook)

Cover 1
Table of contents 8
Preface 6
Contributors 18
Chapter 1. Advances in our Understanding of Neurodegeneration 24
INTRODUCTION 24
BASIC PROCESSES COMMON TO NEURODEGENERATION 24
NEURONAL DEATH – THE FINAL PATHWAY 59
CHALLENGES OF APOPTOSIS IN NEURODEGENERATION 61
CONCLUSION 65
REFERENCES 66
Chapter 2. Mitochondrial Mutagenesis in the Brain in Forensic and Pathological Research 82
INTRODUCTION 82
MITOCHONDRIAL DNA DAMAGE AND REPAIR 83
MAINTENANCE 93
MUTAGENESIS IN THE BRAIN 96
REFERENCES 102
Chapter 3. Genetic and Environmental Factors in Neurodegenerative Diseases 112
CAUSATIVE GENES IN NEURODEGENERATION 112
ENVIRONMENTAL FACTORS AND NEURODEGENERATION 115
SUSCEPTIBILITY GENES IN NEURODEGENERATION 119
OXIDATIVE STRESS 121
APOPTOSIS 126
AGING 128
CONCLUSIONS 129
REFERENCES 130
Chapter 4. Nitric Oxide and Cellular Stress Response in Brain Aging and Neurodegenerative Disorders 138
INTRODUCTION 138
NITRIC OXIDE 139
HEME OXYGENASE 143
CONCLUSIONS AND PERSPECTIVES 150
ACKNOWLEDGMENTS 151
REFERENCES 151
Chapter 5. Oxidative Stress and Radiation-Induced Late Normal Tissue Injury 158
INTRODUCTION 158
RADIATION-INDUCED LATE EFFECTS 159
REACTIVE OXYGEN/NITROGEN OXIDE SPECIES (ROS/RNOS) 164
RADIATION-INDUCED INCREASE IN ROS/RNOS GENERATION 166
THE ROLE OF OXIDATIVE STRESS IN RADIATION-INDUCED LATE EFFECTS 167
TREATMENT OF RADIATION-INDUCED LATE INJURY WITH RAS BLOCKADE 171
PUTATIVE MEDIATORS OF CHRONIC OXIDATIVE STRESS: ANG II AND IONIZING RADIATION 174
ACKNOWLEDGMENTS 175
REFERENCES 175
Chapter 6. The Cell Cycle and Oxidative Neuronal Cell Death 188
INTRODUCTION 188
THE TERMINALLY DIFFERENTIATED NEURON AND THE CELL DIVISION 189
THE CELL CYCLE AND CHECKPOINT FUNCTION 190
CELL CYCLE REGULATORS AND NEURODEGENERATION 192
OXIDATIVE STRESS INDUCTION OF THE CELL CYCLE 196
IS THE CELL CYCLE REQUIRED FOR OXIDATIVE STRESS-INDUCED DEATH? 197
CONCLUSION 198
ACKNOWLEDGMENTS 200
REFERENCES 200
Chapter 7. Redox Imbalance 206
INTRODUCTION: FREE RADICALS AND OXIDATIVE STRESS 206
FACTORS CONTRIBUTING TO THE GENERATION OF OXIDATIVE STRESS (OS) 207
INTERACTION OF ROS WITH GENETIC INFLUENCES, PROTEIN AGGREGATION AND LEWY BODIES (LBS) 211
MITOCHONDRIAL DYSFUNCTION 212
CONSEQUENCES OF REDOX IMBALANCE 214
CONCLUSION AND THERAPEUTIC OUTLOOK 215
REFERENCES 216
Chapter 8. Genes and Oxidative Stress in Sporadic and Familial Parkinsonism: cDNA Microarray Studies 224
INTRODUCTION 224
CELL CULTURE MODELS 225
ANIMAL MODELS 227
HUMAN POST-MORTEM PD SUBJECTS 233
CONCLUSION 238
ACKNOWLEDGEMENT 238
REFERENCES 238
Chapter 9. Down Syndrome, Antioxidant Balance and the Gene Dosage EffectŽ Hypothesis 242
INTRODUCTION 242
ANALYSIS OF THE HSA21 GENE, CU/ZN-SUPEROXIDE DISMUTASE-1 (SOD1) AND ITS RELATIONSHIP TO THE ANTIOXIDANT PATHWAY 243
EVIDENCE FOR THE INVOLVEMENT OF AN ALTERED ANTIOXIDANT PATHWAY IN DOWN SYNDROME (DS) 246
CONCLUSIONS/DISCUSSION AND FUTURE DIRECTIONS FOR THERAPEUTIC INTERVENTIONS 252
REFERENCES 253
Chapter 10. The Role of Levodopa in the Chronic Neurodegenerative Disorder – Parkinson’s Disease 260
INTRODUCTION 260
DIAGNOSIS 260
TREATMENT WITH LEVODOPA 261
MOTOR COMPLICATIONS 262
LEVODOPA-INDUCED ELEVATION OF HOMOCYSTEINE 263
THERAPY OF INCREASED HOMOCYSTEINE LEVELS IN PD PATIENTS 264
IS LEVODOPA ADMINISTRATION TOXIC IN CLINICAL PRACTICE? 265
CONCLUSION 265
REFERENCES 266
Chapter 11. Reactive Oxygen Metabolites (ROMs) as an Index of Oxidative Stress in Obstructive Sleep Apnea Patients 270
OBSTRUCTIVE SLEEP APNEA (OSA) SYNDROME 270
OXIDATION AND REDUCTION – PRO-OXIDANTS AND ANTIOXIDANTS 274
HYPOXIA/REOXYGENATION INJURY (H/R) 278
D-ROM TEST 280
CONCLUSION 281
REFERENCES 282
Chapter 12. The Key Role of Oxidative Stress in Alzheimer’s Disease 290
INTRODUCTION 290
ENERGETIC METABOLISM DEFICIENCY IN ALZHEIMER’S DISEASE 291
OXIDATIVE STRESS IN ALZHEIMER’S DISEASE 292
SOURCES OF OXIDATIVE STRESS IN ALZHEIMER’S DISEASE 294
ALZHEIMER’S DISEASE LESIONS: CAUSE OR CONSEQUENCE OF OXIDATIVE STRESS? 296
CONCLUSIONS 299
REFERENCES 299
Chapter 13. The Role of Oxidative Stress in the Pathogenesis of Multiple Sclerosis: Current State 306
INTRODUCTION 306
OXIDATIVE STRESS IN THE CNS 307
OXIDATIVE STRESS AND INFLAMMATION 307
OXIDATIVE STRESS IN MS 309
ANTIOXIDANTS AS POSSIBLE TREATMENT FOR MS 311
EXPERIMENTAL STUDIES 312
CLINICAL STUDIES 313
CONCLUDING REMARKS AND FUTURE STRATEGIES 314
REFERENCES 314
Chapter 14. Oxidative Stress and Neuroinflammation in Alzheimer’s Disease and Amyotrophic Lateral Sclerosis: From Biology to Therapeutic Strategies 320
NEUROINFLAMMATION – A COMMON FEATURE OF MOST AGE-RELATED NEURODEGENERATIVE DISEASES 320
NEUROINFLAMMATION AND ALZHEIMER’S DISEASE 320
ANTI-AMYLOIDOGENIC PROPERTIES OF NSAIDS – A NOVEL MECHANISM OF ACTION 321
MECHANISM UNDERLYING THE REDUCTION IN Aß GENERATION BY NSAIDS 322
NSAIDS AND CLINICAL TRIALS 322
ANTIOXIDANT TREATMENT AND ALZHEIMER’S DISEASE 327
ANTIOXIDANT CLINICAL TRIALS USING ALZHEIMER’S DISEASE PATIENTS 327
NEUROINFLAMMATION, OXIDATIVE STRESS, AND ALS 328
CONCLUDING REMARKS 328
ACKNOWLEDGMENTS 329
REFERENCES 329
Chapter 15. Oxidative Stress in Stroke 336
INTRODUCTION 336
THERAPEUTIC STRATEGIES WITH ANTIOXIDANTS IN ACUTE AND CHRONIC PHASES AFTER STROKE 366
CONCLUDING REMARKS 378
REFERENCES 379
Chapter 16. Hyperoxidation of the Two Catecholamines, Dopamine and Adrenaline 392
DOPAMINE AND DOPACHROME 392
ADRENALINE AND ADRENOCHROME 398
CONCLUSIONS 402
REFERENCES 402
Chapter 17. The Role of Metals and their Effect on Oxidative Stress in Amyotrophic Lateral Sclerosis 406
INTRODUCTION 406
OXIDATIVE STRESS AND ALS 407
COPPER HOMEOSTASIS AND ALS 410
IRON HOMEOSTASIS AND ALS 413
COPPER AND IRON: THE DEVIL’S PAIR? 415
CONCLUSIONS 416
REFERENCES 416
Chapter 18. Neurotransmission, Oxidative Stress, and Coexistence of Neurotransmitters in Parkinson’s Disease 422
INTRODUCTION 422
MATERIAL AND METHODS 425
CONCLUSIONS 447
REFERENCES 448
Chapter 19. Manganese-Induced Oxidative Stress 456
INTRODUCTION 456
SOURCES OF MANGANESE 457
ESSENTIALITY, ABSORPTION, AND TRANSPORT 457
TOXICITY 461
MANGANESE-INDUCED OXIDATIVE STRESS 463
REFERENCES 466
Chapter 20. Prospects for Antioxidant Therapy in Mild Cognitive Impairment and Alzheimer’s Disease 474
INTRODUCTION 474
THE EARLY INVOLVEMENT OF OXIDATIVE STRESS IN THE PATHOGENESIS OF AD 475
ANTI-OXIDATIVE STRATEGY FOR AD: LESSONS FROM VITAMIN E STUDIES 478
ANTI-OXIDATIVE STRATEGY FOR AD: TARGETING MODIFIABLE RISK FACTORS 481
CONCLUSION 483
REFERENCES 483
Chapter 21. An Assessment of the Chances of Antiapoptotic Drug Therapy in Patients with Neurodegenerative Disorders 490
APOPTOSIS AND OTHER MODES OF CELL DEATH 490
EVIDENCE FOR A ROLE OF PCD IN ND 496
DEVELOPMENT OF ANTIAPOPTOTIC DRUGS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (ND) 504
THE FIRST TWO ANTIAPOPTOTIC COMPOUNDS FAILED IN CLINICAL TRIALS 504
CONCLUSIONS 513
REFERENCES 515
Chapter 22. Role of Antioxidant Activity of Estrogens in their Potent Neuroprotection 526
INTRODUCTION 526
ACKNOWLEDGMENTS 536
REFERENCES 536
Chapter 23. Diet, Herbs, and Nutritional Protection against Oxidative Stress in Neurological Diseases 548
INTRODUCTION 548
CONCLUSIONS 559
REFERENCES 559
Chapter 24. Diabetic Neuropathy: Pathogenesis and Treatment 566
INTRODUCTION 566
TREATMENT OF DIABETIC NEUROPATHY 577
NEUROSENSORY TESTING IN DIABETIC NEUROPATHY 589
REFERENCES 595
Chapter 25. Green and Black Tea in Brain Protection 604
INTRODUCTION 604
REFERENCES 623
Chapter 26. Environmental and Genetic Interactions: Key to Sporadic Parkinson’s Disease? 630
INTRODUCTION 630
CONCLUDING REMARKS 637
ACKNOWLEDGMENT 638
REFERENCES 639
Chapter 27. Prevention and Therapy of Neurodegenerative Disorders: Role of Nutritional Antioxidants 644
MAJOR NEURODEGENERATIVE DISORDERS 644
NATURAL DIETARY ANTIOXIDANTS 648
ROS, NF- B, AND NEURODEGENERATIVE DISORDERS 656
ALZHEIMER’S DISEASE, OXIDATIVE STRESS, NF- B, AND ANTIOXIDANTS 658
PARKINSON’S DISEASE, OXIDATIVE STRESS, NF- , AND ANTIOXIDANTS 661
AMYOTROPHIC LATERAL SCLEROSIS, OXIDATIVE STRESS, NF- B, AND ANTIOXIDANTS 665
CONCLUSIONS 667
ACKNOWLEDGMENTS 668
REFERENCES 669
Chapter 28. Genetics of Parkinson’s Disease 686
INTRODUCTION 686
CAUSATIVE GENES FOR FAMILIAL PD 688
SUSCEPTIBILITY GENES FOR PD 698
GENETIC IMPLICATIONS FOR PD 710
ACKNOWLEDGMENT 710
REFERENCES 711
Chapter 29. Biomarkers of Hypoxic Brain Injury 722
INTRODUCTION 722
CONCLUSIONS 733
REFERENCES 734
Chapter 30. Role of Selenium, Iron, Copper, and Zinc in Parkinsonism 742
INTRODUCTION 742
PATIENTS AND METHODS 744
RESULTS 745
DISCUSSION 746
REFERENCES 754
Chapter 31. Oxidative Stress in Phagocytic Cells: Changes with Age and Effect of Melatonin 760
INTRODUCTION 760
PINEALECTOMY, BURSECTOMY, AND THE IMMUNE SYSTEM 767
CONCLUSIONS: FUTURE HORIZON 779
REFERENCES 780
Index 786