This first volume starts with an overview on current perspectives in genetic research and on the molecular mechanisms of neurodegeneration. This is followed by a selection of hot topics in pathophysiological research, from molecular studies to system-level investigations based on in vivo electrophysiological recordings and neurocomputational methods.
Complete overview of hot topics and approaches to current PD research, from molecules, to brain circuits, to clinical and therapeutic applications. Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research. All chapters include comprehensive background information and are written in a clear form that is accessible also to the non-specialist.
1. Introduction 2. Identification of monogenic forms of PD by positional cloning strategies 3. Autosomal-recessive parkinsonism 4. Rare genetic variants causing or pre-disposing to PD 5. Common risk variants for PD: candidate gene and whole genome association studies 6. Future strategies 7. Conclusion 8. The impact of genetic research on our understanding of Parkinson’s disease 9. Introduction 10. Dominantly inherited mutations 11. Conclusion 12. Acknowledgements 13. Unravelling the role of defective genes 14. Introduction 15. Summary 16. Acknowledgements 17. What causes the death of dopaminergic neurons in Parkinson’s disease? 18. Pan-cellular risk factors in Parkinson’s disease 19. Cell-specific risk factors in PD 20. Do other types of neuron that succumb in PD share these risk factors? 21. Is there an interaction between risk factors? 22. Can dihydropyridines be therapeutically effective? 23. Epidemiological support for cell-specific risk factors 24. Unanswered questions 25. Conclusions 26. Intracellular signalling pathways in dopamine cell death and axonal degeneration 27. PCD in dopamine neurons: major pathways of neuron destruction 28. Intracellular signalling pathways for dopaminergic axonal degeneration 29. PCD in dopamine neurons: is it only downstream? 30. PCD in dopamine neurons: is it the default mode? 31. Summary and conclusions 32. Acknowledgements 33. Control of mitochondrial integrity in Parkinson’s disease 34. Mitochondrial fusion and fission machinery 35. Mitochondrial motility 36. Mitophagy 37. Conclusions 38. Acknowledgement 39. Role of post-translational modifications in modulating the structure, function and toxicity of α-synuclein 40. Introduction 41. Structural and biochemical properties of α-syn 42. The rate of α-synuclein fibrillization is affected by several factors that may be relevant to PD 43. Phosphorylation 44. Truncations 45. Ubiquitination 46. Conclusions 47. The role of dopamine in modulating the structure and function of striatal circuits 48. Introduction 49. Acute dopaminergic modulation of striatal MSN excitability 50. LTD at glutamatergic synapses on MSNs 51. LTP at glutamatergic synapses on MSNs 52. Dendritic excitability and synaptic plasticity 53. Homeostatic plasticity in PD models 54. Concluding remarks 55. Acknowledgements 56. Assemblies of glutamate receptor subunits with post-synaptic density proteins and their alterations in Parkinson’s disease 57. Alterations of the NMDA receptor complex in experimental PD 58. Alterations of AMPA receptors in experimental PD 59. Pathological synaptic plasticity in the striatum: implications for PD 60. Alterations of the glutamatergic synapse in l-DOPA-induced dyskinesia 61. NMDA receptor antagonist in experimental PD and in dyskinesia 62. AMPA receptor modulation in PD therapy 63. Functional and molecular cross-talk between D1 and NMDA receptors: role in physiological synaptic transmission, in experimental PD and in l-DOPA-induced dyskinesia 64. Conclusions 65. Pathophysiological roles for purines 66. Adenosine receptors: localization and functional interactions with dopamine receptors 67. Receptor–receptor interaction: heterodimeric complexes as basis for new anti-parkinsonian therapies 68. Role of adenosine receptors in neuroprotection 69. Epidemiology and clinical trials of adenosine antagonists 70. Clinical trials of A2A antagonists for PD 71. Urate as a novel target for neuroprotection 72. Acknowledgements 73. Maladaptive striatal plasticity in l-DOPA-induced dyskinesia 74. Introduction 75. Molecular alterations associated with LID 76. Towards a unifying molecular interpretation of LID 77. ‘Too much’ molecular plasticity leads to plasticity failure 78. Concluding remarks 79. Acknowledgements 80. Effects of GPi and STN inactivation on physiological, motor, cognitive and motivational processes in animal models of Parkinson’s disease 81. Introduction 82. GPi manipulation in PD 83. STN manipulation in PD 84. General conclusion 85. Acknowledgements 86. Computational physiology of the basal ganglia in Parkinson’s disease 87. Introduction 88. Methods 89. Results 90. Discussion 91. Acknowledgements 92. Neurocomputational models of motor and cognitive deficits in Parkinson’s disease 93. Introduction 94. Neural network models of basal ganglia 95. Architecture of basal ganglia models 96. Cognitive learning deficits 97. Motor impairments 98. Conclusion and outlook 99. Acknowledgements
This first volume starts with an overview on current perspectives in genetic research and on the molecular mechanisms of neurodegeneration. This is followed by a selection of hot topics in pathophysiological research, from molecular studies to system-level investigations based on in vivo electrophysiological recordings and neurocomputational methods.
Complete overview of hot topics and approaches to current PD research, from molecules, to brain circuits, to clinical and therapeutic applications. Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research. All chapters include comprehensive background information and are written in a clear form that is accessible also to the non-specialist.
1. Introduction 2. Identification of monogenic forms of PD by positional cloning strategies 3. Autosomal-recessive parkinsonism 4. Rare genetic variants causing or pre-disposing to PD 5. Common risk variants for PD: candidate gene and whole genome association studies 6. Future strategies 7. Conclusion 8. The impact of genetic research on our understanding of Parkinson’s disease 9. Introduction 10. Dominantly inherited mutations 11. Conclusion 12. Acknowledgements 13. Unravelling the role of defective genes 14. Introduction 15. Summary 16. Acknowledgements 17. What causes the death of dopaminergic neurons in Parkinson’s disease? 18. Pan-cellular risk factors in Parkinson’s disease 19. Cell-specific risk factors in PD 20. Do other types of neuron that succumb in PD share these risk factors? 21. Is there an interaction between risk factors? 22. Can dihydropyridines be therapeutically effective? 23. Epidemiological support for cell-specific risk factors 24. Unanswered questions 25. Conclusions 26. Intracellular signalling pathways in dopamine cell death and axonal degeneration 27. PCD in dopamine neurons: major pathways of neuron destruction 28. Intracellular signalling pathways for dopaminergic axonal degeneration 29. PCD in dopamine neurons: is it only downstream? 30. PCD in dopamine neurons: is it the default mode? 31. Summary and conclusions 32. Acknowledgements 33. Control of mitochondrial integrity in Parkinson’s disease 34. Mitochondrial fusion and fission machinery 35. Mitochondrial motility 36. Mitophagy 37. Conclusions 38. Acknowledgement 39. Role of post-translational modifications in modulating the structure, function and toxicity of α-synuclein 40. Introduction 41. Structural and biochemical properties of α-syn 42. The rate of α-synuclein fibrillization is affected by several factors that may be relevant to PD 43. Phosphorylation 44. Truncations 45. Ubiquitination 46. Conclusions 47. The role of dopamine in modulating the structure and function of striatal circuits 48. Introduction 49. Acute dopaminergic modulation of striatal MSN excitability 50. LTD at glutamatergic synapses on MSNs 51. LTP at glutamatergic synapses on MSNs 52. Dendritic excitability and synaptic plasticity 53. Homeostatic plasticity in PD models 54. Concluding remarks 55. Acknowledgements 56. Assemblies of glutamate receptor subunits with post-synaptic density proteins and their alterations in Parkinson’s disease 57. Alterations of the NMDA receptor complex in experimental PD 58. Alterations of AMPA receptors in experimental PD 59. Pathological synaptic plasticity in the striatum: implications for PD 60. Alterations of the glutamatergic synapse in l-DOPA-induced dyskinesia 61. NMDA receptor antagonist in experimental PD and in dyskinesia 62. AMPA receptor modulation in PD therapy 63. Functional and molecular cross-talk between D1 and NMDA receptors: role in physiological synaptic transmission, in experimental PD and in l-DOPA-induced dyskinesia 64. Conclusions 65. Pathophysiological roles for purines 66. Adenosine receptors: localization and functional interactions with dopamine receptors 67. Receptor–receptor interaction: heterodimeric complexes as basis for new anti-parkinsonian therapies 68. Role of adenosine receptors in neuroprotection 69. Epidemiology and clinical trials of adenosine antagonists 70. Clinical trials of A2A antagonists for PD 71. Urate as a novel target for neuroprotection 72. Acknowledgements 73. Maladaptive striatal plasticity in l-DOPA-induced dyskinesia 74. Introduction 75. Molecular alterations associated with LID 76. Towards a unifying molecular interpretation of LID 77. ‘Too much’ molecular plasticity leads to plasticity failure 78. Concluding remarks 79. Acknowledgements 80. Effects of GPi and STN inactivation on physiological, motor, cognitive and motivational processes in animal models of Parkinson’s disease 81. Introduction 82. GPi manipulation in PD 83. STN manipulation in PD 84. General conclusion 85. Acknowledgements 86. Computational physiology of the basal ganglia in Parkinson’s disease 87. Introduction 88. Methods 89. Results 90. Discussion 91. Acknowledgements 92. Neurocomputational models of motor and cognitive deficits in Parkinson’s disease 93. Introduction 94. Neural network models of basal ganglia 95. Architecture of basal ganglia models 96. Cognitive learning deficits 97. Motor impairments 98. Conclusion and outlook 99. Acknowledgements
