Oxidative Stress and Neurodegenerative Disorders
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Table of contents
- Cover
- Table of contentsvii
- Prefacev
- Contributorsxvii
- Chapter 1. Advances in our Understanding of Neurodegeneration1
- INTRODUCTION1
- BASIC PROCESSES COMMON TO NEURODEGENERATION1
- NEURONAL DEATH – THE FINAL PATHWAY36
- CHALLENGES OF APOPTOSIS IN NEURODEGENERATION38
- CONCLUSION42
- REFERENCES43
- Chapter 2. Mitochondrial Mutagenesis in the Brain in Forensic and Pathological Research59
- INTRODUCTION59
- MITOCHONDRIAL DNA DAMAGE AND REPAIR60
- MAINTENANCE70
- MUTAGENESIS IN THE BRAIN73
- REFERENCES79
- Chapter 3. Genetic and Environmental Factors in Neurodegenerative Diseases89
- CAUSATIVE GENES IN NEURODEGENERATION89
- ENVIRONMENTAL FACTORS AND NEURODEGENERATION92
- SUSCEPTIBILITY GENES IN NEURODEGENERATION96
- OXIDATIVE STRESS98
- APOPTOSIS103
- AGING105
- CONCLUSIONS106
- REFERENCES107
- Chapter 4. Nitric Oxide and Cellular Stress Response in Brain Aging and Neurodegenerative Disorders115
- INTRODUCTION115
- NITRIC OXIDE116
- HEME OXYGENASE120
- CONCLUSIONS AND PERSPECTIVES127
- ACKNOWLEDGMENTS128
- REFERENCES128
- Chapter 5. Oxidative Stress and Radiation-Induced Late Normal Tissue Injury135
- INTRODUCTION135
- RADIATION-INDUCED LATE EFFECTS136
- REACTIVE OXYGEN/NITROGEN OXIDE SPECIES (ROS/RNOS)141
- RADIATION-INDUCED INCREASE IN ROS/RNOS GENERATION143
- THE ROLE OF OXIDATIVE STRESS IN RADIATION-INDUCED LATE EFFECTS144
- TREATMENT OF RADIATION-INDUCED LATE INJURY WITH RAS BLOCKADE148
- PUTATIVE MEDIATORS OF CHRONIC OXIDATIVE STRESS: ANG II AND IONIZING RADIATION151
- ACKNOWLEDGMENTS152
- REFERENCES152
- Chapter 6. The Cell Cycle and Oxidative Neuronal Cell Death165
- INTRODUCTION165
- THE TERMINALLY DIFFERENTIATED NEURON AND THE CELL DIVISION166
- THE CELL CYCLE AND CHECKPOINT FUNCTION167
- CELL CYCLE REGULATORS AND NEURODEGENERATION169
- OXIDATIVE STRESS INDUCTION OF THE CELL CYCLE173
- IS THE CELL CYCLE REQUIRED FOR OXIDATIVE STRESS-INDUCED DEATH?174
- CONCLUSION175
- ACKNOWLEDGMENTS177
- REFERENCES177
- Chapter 7. Redox Imbalance183
- INTRODUCTION: FREE RADICALS AND OXIDATIVE STRESS183
- FACTORS CONTRIBUTING TO THE GENERATION OF OXIDATIVE STRESS (OS)184
- INTERACTION OF ROS WITH GENETIC INFLUENCES, PROTEIN AGGREGATION AND LEWY BODIES (LBS)188
- MITOCHONDRIAL DYSFUNCTION189
- CONSEQUENCES OF REDOX IMBALANCE191
- CONCLUSION AND THERAPEUTIC OUTLOOK192
- REFERENCES193
- Chapter 8. Genes and Oxidative Stress in Sporadic and Familial Parkinsonism: cDNA Microarray Studies201
- INTRODUCTION201
- CELL CULTURE MODELS202
- ANIMAL MODELS204
- HUMAN POST-MORTEM PD SUBJECTS210
- CONCLUSION215
- ACKNOWLEDGEMENT215
- REFERENCES215
- Chapter 9. Down Syndrome, Antioxidant Balance and the Gene Dosage EffectŽ Hypothesis219
- INTRODUCTION219
- ANALYSIS OF THE HSA21 GENE, CU/ZN-SUPEROXIDE DISMUTASE-1 (SOD1) AND ITS RELATIONSHIP TO THE ANTIOXID220
- EVIDENCE FOR THE INVOLVEMENT OF AN ALTERED ANTIOXIDANT PATHWAY IN DOWN SYNDROME (DS)223
- CONCLUSIONS/DISCUSSION AND FUTURE DIRECTIONS FOR THERAPEUTIC INTERVENTIONS229
- REFERENCES230
- Chapter 10. The Role of Levodopa in the Chronic Neurodegenerative Disorder – Parkinson’s Disease237
- INTRODUCTION237
- DIAGNOSIS237
- TREATMENT WITH LEVODOPA238
- MOTOR COMPLICATIONS239
- LEVODOPA-INDUCED ELEVATION OF HOMOCYSTEINE240
- THERAPY OF INCREASED HOMOCYSTEINE LEVELS IN PD PATIENTS241
- IS LEVODOPA ADMINISTRATION TOXIC IN CLINICAL PRACTICE?242
- CONCLUSION242
- REFERENCES243
- Chapter 11. Reactive Oxygen Metabolites (ROMs) as an Index of Oxidative Stress in Obstructive Sleep247
- OBSTRUCTIVE SLEEP APNEA (OSA) SYNDROME247
- OXIDATION AND REDUCTION – PRO-OXIDANTS AND ANTIOXIDANTS251
- HYPOXIA/REOXYGENATION INJURY (H/R)255
- D-ROM TEST257
- CONCLUSION258
- REFERENCES259
- Chapter 12. The Key Role of Oxidative Stress in Alzheimer’s Disease267
- INTRODUCTION267
- ENERGETIC METABOLISM DEFICIENCY IN ALZHEIMER’S DISEASE268
- OXIDATIVE STRESS IN ALZHEIMER’S DISEASE269
- SOURCES OF OXIDATIVE STRESS IN ALZHEIMER’S DISEASE271
- ALZHEIMER’S DISEASE LESIONS: CAUSE OR CONSEQUENCE OF OXIDATIVE STRESS?273
- CONCLUSIONS276
- REFERENCES276
- Chapter 13. The Role of Oxidative Stress in the Pathogenesis of Multiple Sclerosis: Current State283
- INTRODUCTION283
- OXIDATIVE STRESS IN THE CNS284
- OXIDATIVE STRESS AND INFLAMMATION284
- OXIDATIVE STRESS IN MS286
- ANTIOXIDANTS AS POSSIBLE TREATMENT FOR MS288
- EXPERIMENTAL STUDIES289
- CLINICAL STUDIES290
- CONCLUDING REMARKS AND FUTURE STRATEGIES291
- REFERENCES291
- Chapter 14. Oxidative Stress and Neuroinflammation in Alzheimer’s Disease and Amyotrophic Lateral297
- NEUROINFLAMMATION – A COMMON FEATURE OF MOST AGE-RELATED NEURODEGENERATIVE DISEASES297
- NEUROINFLAMMATION AND ALZHEIMER’S DISEASE297
- ANTI-AMYLOIDOGENIC PROPERTIES OF NSAIDS – A NOVEL MECHANISM OF ACTION298
- MECHANISM UNDERLYING THE REDUCTION IN Aβ GENERATION BY NSAIDS299
- NSAIDS AND CLINICAL TRIALS299
- ANTIOXIDANT TREATMENT AND ALZHEIMER’S DISEASE304
- ANTIOXIDANT CLINICAL TRIALS USING ALZHEIMER’S DISEASE PATIENTS304
- NEUROINFLAMMATION, OXIDATIVE STRESS, AND ALS305
- CONCLUDING REMARKS305
- ACKNOWLEDGMENTS306
- REFERENCES306
- Chapter 15. Oxidative Stress in Stroke313
- INTRODUCTION313
- THERAPEUTIC STRATEGIES WITH ANTIOXIDANTS IN ACUTE AND CHRONIC PHASES AFTER STROKE343
- CONCLUDING REMARKS355
- REFERENCES356
- Chapter 16. Hyperoxidation of the Two Catecholamines, Dopamine and Adrenaline369
- DOPAMINE AND DOPACHROME369
- ADRENALINE AND ADRENOCHROME375
- CONCLUSIONS379
- REFERENCES379
- Chapter 17. The Role of Metals and their Effect on Oxidative Stress in Amyotrophic Lateral Sclerosis383
- INTRODUCTION383
- OXIDATIVE STRESS AND ALS384
- COPPER HOMEOSTASIS AND ALS387
- IRON HOMEOSTASIS AND ALS390
- COPPER AND IRON: THE DEVIL’S PAIR?392
- CONCLUSIONS393
- REFERENCES393
- Chapter 18. Neurotransmission, Oxidative Stress, and Coexistence of Neurotransmitters in Parkinson??399
- INTRODUCTION399
- MATERIAL AND METHODS402
- CONCLUSIONS424
- REFERENCES425
- Chapter 19. Manganese-Induced Oxidative Stress433
- INTRODUCTION433
- SOURCES OF MANGANESE434
- ESSENTIALITY, ABSORPTION, AND TRANSPORT434
- TOXICITY438
- MANGANESE-INDUCED OXIDATIVE STRESS440
- REFERENCES443
- Chapter 20. Prospects for Antioxidant Therapy in Mild Cognitive Impairment and Alzheimer’s Disease451
- INTRODUCTION451
- THE EARLY INVOLVEMENT OF OXIDATIVE STRESS IN THE PATHOGENESIS OF AD452
- ANTI-OXIDATIVE STRATEGY FOR AD: LESSONS FROM VITAMIN E STUDIES455
- ANTI-OXIDATIVE STRATEGY FOR AD: TARGETING MODIFIABLE RISK FACTORS458
- CONCLUSION460
- REFERENCES460
- Chapter 21. An Assessment of the Chances of Antiapoptotic Drug Therapy in Patients with Neurodegener467
- APOPTOSIS AND OTHER MODES OF CELL DEATH467
- EVIDENCE FOR A ROLE OF PCD IN ND473
- DEVELOPMENT OF ANTIAPOPTOTIC DRUGS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (ND)481
- THE FIRST TWO ANTIAPOPTOTIC COMPOUNDS FAILED IN CLINICAL TRIALS481
- CONCLUSIONS490
- REFERENCES492
- Chapter 22. Role of Antioxidant Activity of Estrogens in their Potent Neuroprotection503
- INTRODUCTION503
- ACKNOWLEDGMENTS513
- REFERENCES513
- Chapter 23. Diet, Herbs, and Nutritional Protection against Oxidative Stress in Neurological Disease525
- INTRODUCTION525
- CONCLUSIONS536
- REFERENCES536
- Chapter 24. Diabetic Neuropathy: Pathogenesis and Treatment543
- INTRODUCTION543
- TREATMENT OF DIABETIC NEUROPATHY554
- NEUROSENSORY TESTING IN DIABETIC NEUROPATHY566
- REFERENCES572
- Chapter 25. Green and Black Tea in Brain Protection581
- INTRODUCTION581
- REFERENCES600
- Chapter 26. Environmental and Genetic Interactions: Key to Sporadic Parkinson’s Disease?607
- INTRODUCTION607
- CONCLUDING REMARKS614
- ACKNOWLEDGMENT615
- REFERENCES616
- Chapter 27. Prevention and Therapy of Neurodegenerative Disorders: Role of Nutritional Antioxidants621
- MAJOR NEURODEGENERATIVE DISORDERS621
- NATURAL DIETARY ANTIOXIDANTS625
- ROS, NF- B, AND NEURODEGENERATIVE DISORDERS633
- ALZHEIMER’S DISEASE, OXIDATIVE STRESS, NF- B, AND ANTIOXIDANTS635
- PARKINSON’S DISEASE, OXIDATIVE STRESS, NF- , AND ANTIOXIDANTS638
- AMYOTROPHIC LATERAL SCLEROSIS, OXIDATIVE STRESS, NF- B, AND ANTIOXIDANTS642
- CONCLUSIONS644
- ACKNOWLEDGMENTS645
- REFERENCES646
- Chapter 28. Genetics of Parkinson’s Disease663
- INTRODUCTION663
- CAUSATIVE GENES FOR FAMILIAL PD665
- SUSCEPTIBILITY GENES FOR PD675
- GENETIC IMPLICATIONS FOR PD687
- ACKNOWLEDGMENT687
- REFERENCES688
- Chapter 29. Biomarkers of Hypoxic Brain Injury699
- INTRODUCTION699
- CONCLUSIONS710
- REFERENCES711
- Chapter 30. Role of Selenium, Iron, Copper, and Zinc in Parkinsonism719
- INTRODUCTION719
- PATIENTS AND METHODS721
- RESULTS722
- DISCUSSION723
- REFERENCES731
- Chapter 31. Oxidative Stress in Phagocytic Cells: Changes with Age and Effect of Melatonin737
- INTRODUCTION737
- PINEALECTOMY, BURSECTOMY, AND THE IMMUNE SYSTEM744
- CONCLUSIONS: FUTURE HORIZON756
- REFERENCES757
- Index763
Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders.
* Contains the latest information on the subject of neurodegenerative disorders
* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems
* Contains the latest information on the subject of neurodegenerative disorders
* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems