Parkinson's Disease: molecular and therapeutic insights from model systems

Parkinson's Disease: molecular and therapeutic insights from model systems

by Richard Nass

ISBN-10: 0123740282

ISBN-13: 9780123740281

Pub. Date: 08/14/2008

Publisher: Elsevier Science

Parkinson’s disease is the second most prevalent neurodegenerative disease and is characterized by the irreversible loss of dopamine neurons. Despite its high prevalence in society and many decades of research, the origin of the pathogenesis and the molecular determinants involved in the disorder has remained elusive. Confounding this issue is the lack of

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Parkinson’s disease is the second most prevalent neurodegenerative disease and is characterized by the irreversible loss of dopamine neurons. Despite its high prevalence in society and many decades of research, the origin of the pathogenesis and the molecular determinants involved in the disorder has remained elusive. Confounding this issue is the lack of experimental models that completely recapitulate the disease state. The identification of a number of genes thought to play a role in the cell death, and development of both toxin and genetic models to explore the function of the genes both in unaffected and diseased cells are now providing new insights into the molecular basis of the neurodegeneration, as well as therapeutic approaches. In this reference, we will describe the advances and the advantages that various invertebrates, cell culture, rodents, and mammals provide in the identification of the molecular components and mechanisms involved in the cell death, and outline the opportunities that these systems provide in drug discovery.

• Comprehensive and critical assessment of the utility of various model systems to identify the molecular components and pathways involved in Parkinson’s disease

• Describes the power of toxin and genetic models to identify novel therapeutic targets and compounds that can be used in PD

• Current overviews of current status of PD research and discovery from bench-to-bedside

• Provides novel insights and views on where the future of PD research may lead

• Provides a powerful teaching tool and template to explore the utility of model systems to identify molecular pathways, molecular targets, and therapeutics that are applicable to a variety of neurological diseases

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Elsevier Science
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7.70(w) x 9.40(h) x 1.50(d)

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Table of Contents

1 Clinical Aspects of Parkinson Disease Stanley Fahn Fahn, Stanley 3

2 Genetics of Parkinson's Disease Owen A. Ross Ross, Owen A. Adam T. Braithwaite Braithwaite, Adam T. Matthew J. Farrer Farrer, Matthew J. 9

3 Neuropathology of Parkinson's Disease Leonard Petrucelli Petrucelli, Leonard Dennisw Dickson Dickson, Dennisw 35

4 Introduction to: Neurotoxin-Based Nonhuman Primate Models of Parkinson's Disease Zhiming Zhang Zhang, Zhiming Don Marshall Gash Gash, Don Marshall 51

5 Systems Level Physiology of the Basal Ganglia, and Pathophysiology of Parkinson's Disease T. Wichmann Wichmann, T. M. R. Delong Delong, M. R. 55

6 Neuroprotection for Parkinson's Disease: Clinically Driven Experimental Design in Non-Human Primates Erwan Bezard Bezard, Erwan 65

7 The Use of Aged Monkeys to Study PD: Important Roles in Pathogenesis and Experimental Therapeutics Yaping Chu Chu, Yaping Jeffrey H. Kordower Kordower, Jeffrey H. 77

8 I-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine-Induced Mammalian Models of Parkinson's Disease: Potential Uses and Misuses of Acute, Sub-Acute, and Chronic Models J. S. Schneider Schneider, J. S. D. Wanderson Wanderson, D. E. Decamp Decamp, E. 87

9 Non-Human Primate Models of Parkinson's Disease and Experimental Therapeutics lOS Giselle M. Petzinger Petzinger, Giselle M. Daniel M. Togasaki Togasaki, Daniel M. Garnik Akopian Akopian, Garnik John P. Walsh Walsh, John P. Michael W. Jakowec Jakowec, Michael W.

10 Rodent Toxin Models of PD: An Overview Vincent Ries Ries, Vincent Robert E. Burke Burke, Robert E. 135

11 The MPTP Mouse Model of Parkinson's Disease: The True, the False, and the Unknown Vernicejackson-Lewis Serge PrzedborskiPrzedborski, Serge 147

12 Acute and Chronic Administration of I-Methyl-4-Phenylpyridinium Patricia K. Sonsalla Sonsalla, Patricia K. Gail D. Zeevalk Zeevalk, Gail D. Dwight C. German German, Dwight C. 159

13 Endogenous Defenses that Protect Dopamine Neurons: Studies with 6-0HDA Models of Parkinson's Disease Rehana K. Leak Leak, Rehana K. Michael J. Zigmond Zigmond, Michael J. 173

14 Complex I Inhibition, Rotenone and Parkinson's Disease Ranjita Betarbet Betarbet, Ranjita J. Timothy Greenamyre Greenamyre, J. Timothy 195

15 Paraquat-Induced Neurodegeneration: A Model of Parkinson's Disease Risk Factors Donato A. Di Monte Di Monte, Donato A. 207

16 Overview: Rodent and Fish Models of Parkinson's Disease William Dauer Dauer, William 221

17 Genetic Models of Familial Parkinson's Disease Mingyao Ying Ying, Mingyao Valina L. Dawson Dawson, Valina L. Ted M. Dawson Dawson, Ted M. 225

18 The Dynamics of a-Synuclein at the Nerve Terminal Doris L. Fortin Fortin, Doris L. Venu M. Nemani Nemani, Venu M. Robert H. Edwards Edwards, Robert H. 237

19 The BAC Transgenic Approach to Study Parkinson's Disease in Mice X. William Yang Yang, X. William Xiao-Hong Lu Lu, Xiao-Hong 247

20 Viral Vectors: A Potent Approach to Generate Genetic Models of Parkinson's Disease Bernard L. Schneider Schneider, Bernard L. Meret N. Gaugler Gaugler, Meret N. Patrick Aebischer Aebischer, Patrick 269

21 Environmental Explorations of Parkinson's Disease using Rodent Genetic Models Marie-Francoise Chesselet Chesselet, Marie-Francoise Pierre-Olivier Fernagut Fernagut, Pierre-Olivier 285

22 [alpha]-Synuclein, CSP[alpha], SNAREs and Neuroprotection in vivo Sreeganga Chandra Chandra, Sreeganga Thomas C. Sudhof Sudhof, Thomas C. 295

23 Insights from Zebrafish PD Models and Their Potentials for Identifying Novel Drug Targets and Therapeutic Compounds su GUO GUO, su 309

24 Parkinson's Disease: Insights from Invertebrates Ellen B. Penney Penney, Ellen B. Brian D. McCabe McCabe, Brian D. 323

25 Drosophila Models for Parkinson's Disease Research Nancy M. Bonini Bonini, Nancy M. 335

26 Caenorhabditis elegans Models of Parkinson's Disease: A Robust Genetic System to Identify and Characterize Endogenous and Environmental Components Involved in Dopamine Neuron Degeneration Richard Nass Nass, Richard Raja S. Seitivari Seitivari, Raja S. 347

27 C. elegans Genetic Strategies to Identify Novel Parkinson's Disease-Associated Therapeutic Targets and Leads Richard Nass Nass, Richard 361

28 Overview: Cell-Based Models of Parkinson's Disease D. James Surmeier Surmeier, D. James 371

29 PC 12 Cells as a Model for Parkinson's Disease Research Cristina Malagelada Malagelada, Cristina Lloyd A. Greene Greene, Lloyd A. 375

30 Dissociated Mesencephalic Cultures: A Research Tool to Model Dopaminergic Cell Death in Parkinson's Disease Myriam Escobar-Khondiker Escobar-Khondiker, Myriam Damien Toulorge Toulorge, Damien Serge Guerreiro Guerreiro, Serge Etienne C. Hirsch Hirsch, Etienne C. Patrick P. Michel Michel, Patrick P. 389

31 Selective Autophagy in the Pathogenesis of Parkinson's Disease Susmita Kaushik Kaushik, Susmita Esther Wong Wong, Esther Ana Maria Cuervo Cuervo, Ana Maria 409

32 The Role of LRRK2 Kinase Activity in Cellular PD Models Mark R. Cookson Cookson, Mark R. Elisa Greggio Greggio, Elisa Patrick Lewis Lewis, Patrick 423

33 Using Yeast as a Model System for the Genetic Dissection of [alpha]-Synuclein Toxicity Vicente Sancenon Sancenon, Vicente Sue-Ann Lee Lee, Sue-Ann Paul J. Muchowski Muchowski, Paul J. 433

34 The Role of the Foxa2 Gene in the Birth and Death of Dopamine Neurons Raja Kittappa Kittappa, Raja Wendy Chang Chang, Wendy Ronald McKay McKay, Ronald 449

35 Embryonic Stem Cell-Based Models of Parkinson's Disease Mark J. Tomishima Tomishima, Mark J. Lorenz Studer Studer, Lorenz 461

36 Neuroprotective and Neurotoxic Properties of [alpha]-Synuclein in Cell Culture Models of Dopaminergic Degeneration Faneng Sun Sun, Faneng Vellareddy Anantharam Anantharam, Vellareddy Huajun Jin Jin, Huajun Danhui Zhang Zhang, Danhui Arthi Kanthasamy Kanthasamy, Arthi Anumantha G. Kanthasamy Kanthasamy, Anumantha G. 475

37 Postnatally Derived Ventral Midbrain Dopamine Neuron Cultures as a Model System for Studying Neurotoxicity and Parkinson's Disease David Sulzer Sulzer, David Louis-Eric Trudeau Trudeau, Louis-Eric Stephen Rayport Rayport, Stephen 491

38 Yeast Cells as a Discovery Platform for Parkinson's Disease and Other Protein Misfolding Diseases Karen L.Allendoerfer Allendoerfer, Karen L. Linhui Julie Su Su, Linhui Julie Susan Lindquist Lindquist, Susan 505

39 Overview of Cell-Free Systems for the Study of Parkinson's Disease Chun Zhou Chun, Zhou 539

40 Microglial Activation in a Mouse Model of [alpha]-Synuclein Overexpression Kathleen A. Maguire-Zeiss Maguire-Zeiss, Kathleen A. Xiaomin Su Su, Xiaomin Howard J. Federoff Federoff, Howard J. 545

41 Purification and Quantification of Neural [alpha]-Synuclein: Relevance for Pathogenesis and Biomarker Development Brit Mollenhauer Mollenhauer, Brit Michael G. Schlossmacher Schlossmacher, Michael G. 559

42 Protein Folding and Aggregation in in vitro Models of Parkinson's disease: Structure and Function of [alpha]-synuclein David Eliezer Eliezer, David 575

43 The Use of Cell-Free Systems to Characterize Parkinson's Disease-Related Gene Products Jean-Christophe Rochet Rochet, Jean-Christophe Jeremy L. Schieler Schieler, Jeremy L. 597

Index 629

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