Bjorklund / Cenci-Nilsson Recent Advances in Parkinsons Disease

Part I: Basic Research
1. Auflage 2010
ISBN: 978-0-444-53624-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 183, 332 Seiten

Reihe: Progress in Brain Research

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

Autoren/Hrsg.

Bjorklund, Anders

Cenci-Nilsson, Angela

Inhaltsverzeichnis

2;Progress in Brain Research;2
3;Copyright;5
4;List of Contributors;6
5;Preface;10
6;Contents;12
7;Section I. Genetic and molecular mechanisms of neurodegeneration in PD;14
7.1;Chapter 1. Identifying PD-causing genes and genetic susceptibility factors: current approaches and future prospects;16
7.1.1;Abstract;16
7.1.2;Keywords;16
7.1.3;Introduction;16
7.1.4;Identification of monogenic forms of PD by positional cloning strategies;17
7.1.5;Autosomal-recessive parkinsonism;21
7.1.6;Rare genetic variants causing or pre-disposing to PD;22
7.1.7;Future strategies;27
7.1.8;Conclusion;29
7.1.9;Abbreviations;29
7.1.10;References;29
7.2;Chapter 2. The impact of genetic research on our understanding of Parkinson’s disease;34
7.2.1;Abstract;34
7.2.2;Keywords;34
7.2.3;Introduction;34
7.2.4;Dominantly inherited mutations;36
7.2.5;Conclusion;47
7.2.6;Acknowledgements;47
7.2.7;Abbreviations;47
7.3;Chapter 3. Unravelling the role of defective genes;56
7.3.1;Abstract;56
7.3.2;Keywords;56
7.3.3;Introduction;56
7.3.4;Summary;65
7.3.5;Acknowledgements;66
7.3.6;Abbreviations;66
7.3.7;References;66
7.4;Chapter 4.What causes the death of dopaminergic neuronsin Parkinson’s disease?;72
7.4.1;Abstract;72
7.4.2;Pan-cellular risk factors in Parkinson’s disease;72
7.4.3;Cell-specific risk factors in PD;74
7.4.4;Do other types of neuron that succumb in PD share these risk factors?;78
7.4.5;Is there an interaction between risk factors?;79
7.4.6;Can dihydropyridines be therapeutically effective?;80
7.4.7;Epidemiological support for cell-specific riskfactors;82
7.4.8;Unanswered questions;84
7.4.9;Conclusions;85
7.4.10;Abbreviations;86
7.4.11;References;86
7.5;Chapter 5. Intracellular signalling pathways in dopamine cell death and axonal degeneration;92
7.5.1;Abstract;92
7.5.2;Keywords;92
7.5.3;PCD in dopamine neurons: major pathways of neuron destruction;93
7.5.4;Intracellular signalling pathways for dopa minergicaxonal degeneration;96
7.5.5;PCD in dopamine neurons: is it only downstream?;100
7.5.6;PCD in dopamine neurons: is it the default mode?;102
7.5.7;Summary and conclusions;104
7.5.8;Acknowledgements;104
7.5.9;Abbreviations;104
7.5.10;References;105
7.6;Chapter 6. Control of mitochondrial integrity in Parkinson’s disease;112
7.6.1;Abstract:;112
7.6.2;Keywords;112
7.6.3;Mitochondrial fusion and fission machinery;113
7.6.4;Mitochondrial motility;116
7.6.5;Mitophagy;117
7.6.6;Conclusions;120
7.6.7;Acknowledgement;121
7.6.8;Abbreviations;121
7.6.9;References;122
7.7;Chapter 7. Role of post-translational modifications in modulating the structure, function and toxicity a-synuclein: implications for Parkinson’s disease pathogenesis and therapies;128
7.7.1;Abstract;128
7.7.2;Keywords;128
7.7.3;Introduction;128
7.7.4;Structural and biochemical properties of a-syn;129
7.7.5;The rate of a-synuclein fibrillization is affected by several factors that may be relevant to PD;130
7.7.6;Phosphorylation;130
7.7.7;Truncations;139
7.7.8;Ubiquitination;145
7.7.9;Conclusions;149
7.7.10;Abbreviations;153
7.7.11;References;153
8;Section IICellular and system-level pathophysiologyof the basal ganglia in PD;160
8.1;Chapter 8. The role of dopamine in modulating the structure and function of striatal circuits;162
8.1.1;Abstract;162
8.1.2;Keywords;162
8.1.3;Introduction;162
8.1.4;Acute dopaminergic modulation of striatal MSN excitability;163
8.1.5;LTD at glutamatergic synapses on MSNs;165
8.1.6;LTP at glutamatergic synapses on MSNs;168
8.1.7;Dendritic excitability and synaptic plasticity;169
8.1.8;Homeostatic plasticity in PD models;171
8.1.9;Concluding remarks;174
8.1.10;Acknowledgements;176
8.1.11;Abbreviations;176
8.1.12;References;176
8.2;Chapter 9. Assemblies of glutamate receptor subunits withpost-synaptic density proteins and their alterationsin Parkinson’s disease;182
8.2.1;Abstract;182
8.2.2;Keywords;183
8.2.3;Alterations of the NMDA receptor complex inexperimental PD;183
8.2.4;Alterations ofAMPAreceptors in experimental PD;185
8.2.5;Pathological synaptic plasticity in the striatum:implications for PD;186
8.2.6;Alterations of the glutamatergic synapse inL-DOPA-induced dyskinesia;187
8.2.7;NMDA receptor antagonist in experimental PDand in dyskinesia;188
8.2.8;AMPA receptor modulation in PD therapy;188
8.2.9;Functional and molecular cross-talk between D1 and NMDA receptors: role in physiological synaptic transmission, in experimental PD and in L-DOPA-induced dyskinesia;189
8.2.10;Conclusions;191
8.2.11;Abbreviations;191
8.2.12;References;191
8.3;Chapter 10. Pathophysiological roles for purines: adenosine, caffeine and urate;196
8.3.1;Abstract;196
8.3.2;Keywords;196
8.3.3;Adenosine receptors: localization and functional interactions with dopamine receptors;196
8.3.4;Receptor–receptor interaction: heterodimeric complexes as basis for new anti-parkinsonian therapies;197
8.3.5;Role of adenosine receptors in neuroprotection;200
8.3.6;Epidemiology and clinical trials of adenosine antagonists;206
8.3.7;Clinical trials of A2A antagonists for PD;208
8.3.8;Urate as a novel target for neuroprotection;211
8.3.9;Acknowledgements;213
8.3.10;Abbreviations;213
8.3.11;References;214
9;Chapter 11. Maladaptive striatal plasticity in L-DOPA-induced dyskinesia;222
9.1;Abstract;222
9.2;Keywords;222
9.3;Introduction;222
9.4;Molecular alterations associated with LID;227
9.5;Towards a unifying molecular interpretationof LID;232
9.6;‘Too much’ molecular plasticity leads to plasticity failure;237
9.7;Concluding remarks;238
9.8;Acknowledgements;238
9.9;Abbreviations;239
9.10;References;239
10;Chapter 12. Effects of GPi and STN inactivation on physiological, motor, cognitive and motivational processes in animal models of Parkinson’s disease;248
10.1;Abstract;248
10.2;Keywords;248
10.3;Introduction;248
10.4;GPi manipulation in PD;250
10.5;STN manipulation in PD;253
10.6;General conclusion;263
10.7;Acknowledgements;264
10.8;Abbreviations;264
10.9;References;265
11;Chapter 13. Computational physiology of the basal ganglia in Parkinson’s disease;272
11.1;Abstract;272
11.2;Keywords;273
11.3;Introduction;273
11.4;Methods;274
11.5;Results;277
11.6;Acknowledgements;284
11.7;Abbreviations;284
11.8;References;284
12;Chapter 14. Neurocomputational models of motor and cognitive deficits in Parkinson’s disease;288
12.1;Abstract;288
12.2;Keywords;288
12.3;Introduction;288
12.4;Neural network models of basal ganglia;289
12.5;Architecture of basal ganglia models;290
12.6;Cognitive learning deficits;293
12.7;Motor impairments;296
12.8;Conclusion and outlook;303
12.9;Acknowledgements;303
12.10;Abbreviations;303
12.11;References;303
13;Subject Index;312