Neurodegeneration and Neuroprotection in Parkinson's Disease
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Table of contents
- Cover
- Contentsv
- Contributorsix
- Series Prefacexi
- Prefacexiii
- Section 1: Oxidant Stress1
- Chapter 1. Oxidative stress, brain iron and neurodegeneration. Basic principles1
- 1.1 Life in oxygen: a brief comment2
- 1.2 The basic chemistry2
- 1.3 Antioxidant protection9
- 1.4 Brain iron and free radicals11
- 1.5 Oxidative stress: the molecular targets13
- 1.6 Oxidative stress in neurodegenerative diseases15
- 1.7 Conclusions17
- Chapter 2. Pathological evidence for oxidative stress in Parkinson's disease and related degenerativ23
- 2.1 Introduction24
- 2.2 Alterations in iron in PD25
- 2.3 Alterations in mitochondrial function28
- 2.4 Alterations occurring in protective enzyme systems30
- 2.5 Alterations in glutathione content31
- 2.6 Oxidative damage in PD33
- 2.7 Role of levodopa in alterations in indices of oxidative stress34
- 2.8 Oxidative stress and incidental Lewy body disease35
- 2.9 Other related studies36
- 2.10 Which comes first? The horse or the cart?37
- 2.11 Which free radical species are involved in PD?38
- 2.12 Interrelationship of oxidant stress with other mechanisms of cell death40
- 2.13 Conclusions41
- Chapter 3. Treatment of Parkinson's disease with deprenyl (selegiline) and other monoamine oxidase i47
- 3.1 Introduction47
- 3.2 Characteristics of MAOs48
- 3.3 Development of MAO inhibitors48
- 3.4 Deprenyl in PD49
- 3.5 Basis for neuroprotective action50
- 3.6 Clinical trials with MAO inhibitors in early PD51
- 3.7 Neuroprotection versus symptomatic benefit53
- Chapter 4. Iron and neurodegeneration: prospects for neuroprotection55
- 4.1 Introduction55
- 4.2 Iron and the brain57
- 4.3 Iron and neurodegeneration58
- 4.4 Neuroprotection64
- Chapter 5. Nitrone radical traps protect in experimental neurodegenerative diseases69
- 5.1 Introduction70
- 5.2 Background71
- 5.3 Recent experimental observations79
- 5.4 Mechanisms of NRT protective action84
- Chapter 6. Therapeutic effects of nitric oxide synthase inhibition in neuronal injury91
- 6.1 Introduction91
- 6.2 Toxic effects of NO93
- 6.3 NO in ischaemia94
- 6.4 Neuronal NOS inhibitors95
- 6.5 Cellular mechanisms of NO toxicity97
- 6.6 Inducible NOS inhibitors98
- 6.7 Conclusions99
- Section 2: Mitochondrial Toxicity103
- Chapter 7. Mitochondrial dysfunction in neurodegeneration: prospects for neuroprotection103
- 7.1 Introduction104
- 7.2 The mitochondrial respiratory chain and oxidative phosphorylation system104
- 7.3 Diseases of the mitochondrial respiratory chain and mutations of mtDNA110
- 7.4 Parkinson's disease112
- 7.5 Complex I deficiency and the cause of PD115
- 7.6 Mechanism of cell death in PD117
- 7.7 Neuroprotective strategies118
- 7.8 Neuroprotection and the cytotoxic theory120
- 7.9 Conclusions121
- Section 3: Excitatory Neurotoxicity125
- Chapter 8. Bioenergetics and excitotoxicity: the weak excitotoxic hypothesis125
- 8.1 Introduction125
- 8.2 Neuronal energy metabolism127
- 8.3 Metabolic impairment and neurodegenerative disease129
- 8.4 Excitotoxicity and neurodegenerative disease132
- 8.5 The weak excitotoxic hypothesis133
- 8.6 Conclusions139
- Section 4: Calcium Excitatory Toxicity143
- Chapter 9. Calciumions in necrotic and apoptotic cell death143
- 9.1 Introduction143
- 9.2 Intracellular Ca 2+ homeostasis and signalling144
- 9.3 Interference with cell signalling145
- 9.4 Effects of cellular Ca 2+ overload146
- 9.5 Role of Ca 2+ in apoptotic cell killing149
- 9.6 Ca 2+ overload in neuronal cell death151
- 9.7 Concluding remarks155
- Section 5: Trophic Factors159
- Chapter 10. Neurotrophic factors: towards a restorative therapy of Parkinson's disease159
- 10.1 Introduction160
- 10.2 Neurotrophic factors162
- 10.3 Neurotrophic factors and dopaminergic systems167
- 10.4 Neurotrophic factors and non-dopaminergic systems that degenerate in PD173
- 10.5 The challenge of delivering protein growth factors to the brain174
- 10.6 Transplantation and trophic factors in PD176
- 10.7 Conclusion and future directions179
- Section 6: Immune Mechanisms187
- Chapter 11. Immune-mediated cell death and neuroprotection in neurodegenerative diseases187
- 11.1 Introduction187
- 11.2 Amyotrophic lateral sclerosis189
- 11.3 Neurotrophic factors as neuroprotective agents198
- 11.4 Parkinson's disease199
- 11.5 Neuroprotective action of neurotophic factors203
- Section 7: Apoptosis209
- Chapter 12. Reduction of neuronal apoptosis by small molecules: promise for new approaches to neurol209
- 12.1 Nerve cell death and nervous system disorders209
- 12.2 Trophic and trophic-like agents and neuronal apoptosis212
- Index221
Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most divers and rapidly advancing fields in the life sciences. Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological, and therapeutic aspects of chosen research areas.