Parkinson's Disease

Molecular Mechanisms Underlying Pathology

1st Edition - December 19, 2016
Editor: Patrik Verstreken
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 0 3 7 8 3 - 6
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 0 3 8 0 5 - 5

Parkinson’s Disease: Molecular Mechanisms Underlying Pathology explores the molecular pathways at the basis of the cellular defects connected to Parkinson’s disease, the second mo… Read more

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Parkinson’s Disease: Molecular Mechanisms Underlying Pathology explores the molecular pathways at the basis of the cellular defects connected to Parkinson’s disease, the second most common neurodegenerative disease, and the most common movement disorder. This book presents the latest research on the pathways and mechanisms that have been discovered to play a role in Parkinson's pathology.

This focus on mechanisms rather than individual genes allows the contributors to elaborate on overlapping and joint functions of different causative genes. Readers will find descriptions of model systems that present parallels (and differences) between discoveries in different species, demonstrating the importance of multidisciplinary research that spans a broad array of technologies and model organisms.

Written from both a cross-methodology and cross-species perspective, the book provides readers with the current state of knowledge on the molecular biology of Parkinson’s.

List of Contributors
Preface
Chapter 1: The Neurogenetics of Parkinson’s Disease and Putative Links to Other Neurodegenerative Disorders
- Abstract
- 1. Introduction
- 2. Definition of (Genetic) Parkinson’s Disease
- 3. Classification and Nomenclature of Monogenic Parkinson’s Disease
- 4. Monogenic Forms of Parkinson’s Disease and Parkinsonism
- 5. PARK-SNCA
- 6. PARK-LRRK2
- 7. PARK-VPS35
- 8. PARK-Parkin
- 9. PARK-PINK1
- 10. PARK-DJ-1
- 11. Recent Novel Parkinson’s Disease Candidate Genes
- 12. Systematic and Regularly Updated Overview of Parkinson’s Disease Mutations
- 13. Reduced Penetrance and Variable Expressivity of Genetic Parkinson’s Disease
- 14. Genetic Association Studies
- 15. Candidate Gene Studies in Parkinson’s Disease
- 16. Genome-Wide Association Studies
- 17. Gene–Environment Interactions in Parkinson’s Disease
- 18. Lessons Learned From Other Monogenic Neurodegenerative Diseases
- 19. Translational Genetics: From Animal Models to Personalized Treatments
- 20. Most Important Questions for Future Perspectives of PD Neurogenetics
Chapter 2: Electron Transport Chain
- Abstract
- 1. Introduction
- 2. Glycolysis in the Cytosol
- 3. Impact of Electron Transport Chain Dysfunction on Neuronal Function
- 4. What Have the Genetics Taught Us About Electron Transport Chain Dysfunction and the Sporadic Forms of Parkinson’s Disease?
- 5. Correlation Between Findings Obtained Using Different Animal Models
- 6. Therapeutic Pathways Targeting the Electron Transport Chain
- 7. Conclusions
- List of Abbreviations
Chapter 3: Mitochondrial Fission and Fusion
- Abstract
- 1. Introduction
- 2. Fission and Fusion Machinery
- 3. Functions of Fission and Fusion in Neurons
- 4. Fission and Fusion is Linked to Neurodegeneration
- 5. PD Genes and Mitochondrial Morphology
- 6. Mitochondrial Dynamics and Mitochondrial Turnover
- 7. Therapeutic Potential of Targeting Fission and Fusion
- 8. Conclusions
Chapter 4: Axonal Mitochondrial Transport
- Abstract
- 1. Prelude
- 2. On the Distribution of Power: Mitochondria to Match Supply and Demand
- 3. Mitochondrial Movement is Essential for Maintaining a Healthy Mitochondrial Population in Neurons
- 4. A Motor/Adaptor Complex Enables and Regulates Mitochondrial Trafficking
- 5. Linking PD and Mitochondrial Transport: Mitochondrial Dysfunction Causes Mitochondrial Arrest
- 6. Do Other Forms of PD Involve Defects in Mitochondrial Movement?
- 7. Summary: The Virtuous and Vicious Cycles that Link Mitochondrial Transport and Mitochondrial Health
Chapter 5: Mitophagy
- Abstract
- 1. Introduction
- 2. Mitochondrial Quality Control
- 3. PINK1 and Parkin
- 4. PINK1-Parkin-Mediated Mitophagy
- 5. PINK1 and/or Parkin-Independent Selective Mitophagy
- 6. Methods to Detect Mitophagy
- 7. Outstanding Questions
Chapter 6: Autophagy
- Abstract
- 1. Introduction
- 2. Lessons from the Genetics of Parkinsons Disease
- 3. Ageing and Autophagy
- 4. Autophagy in the Nervous System: Friend or Foe?
- 5. Autophagy Induction to Promote Neuronal Survival
- 6. Conclusions
Chapter 7: Endocytosis and Synaptic Function
- Abstract
- 1. Introduction
- 2. The Synaptic Vesicle Cycle and PD
- 3. Exosome Release
- 4. Summary
Chapter 8: Neuroinflammation as a Potential Mechanism Underlying Parkinsons Disease
- Abstract
- 1. Introduction
- 2. The Role of Glial Cells in PD
- 3. Involvement of Proinflammatory Substances and Oxidative Stress in PD
- 4. Infiltration of Lymphocytes in PD
- 5. Involvement of PD-related Genes in Neuroinflammation
- 6. Potential Antiinflammatory Treatments for PD
- 7. Summary and Conclusions
- Acknowledgments
Chapter 9: Protein Translation in Parkinson’s Disease
- Abstract
- 1. Protein Translation and its Regulation in Neurons
- 2. PD-Linked Mutations and Their Impact on Protein Translation
- 3. Protein Translation and Neurotoxicity in Parkinson’s Disease
- 4. Future Directions
- Acknowledgments
Index

Patrik Verstreken

Dr. Verstreken earned his PhD in Developmental Biology at Baylor College of Medicine in Houston, Texas, USA, in the laboratory of Dr. Hugo J. Bellen, after which he did post-doctoral research at Baylor’s Department of Molecular and Human Genetics/Howard Hughes Medical Institute. Since 2007 Dr. Verstreken has served as a Group Leader at VIB and at the University (KU Leuven), Belgium, he was appointed full professor in 2013 and became co-director of the department in 2016. Patrik received an ERC Consolidator Grant in 2015, an ERC Starting Grant in 2010 and a Marie Curie Excellence Grant in 2007 and was appointed as a Francqui Docent in 2009. Dr. Verstreken was chosen to receive the 2014 IBRO-Kemali Prize in recognition of his outstanding work on mechanisms underlying presynaptic transmitter release, and its relevance to neurodegenerative diseases. The IBRO-Kemali International Prize for Research in the Field of Basic and Clinical Neurosciences is awarded every two years to an outstanding researcher under the age of 45 who has made important contributions in the field. In further recognition of his work and outreach activities, Patrik was also recently elected to join the FENS-Kavli network of excellence. Patrik Verstreken’s Laboratory studies neuronal communication in health and disease, by combining fruit fly genetics and molecular biology with electrophysiological measurements of synaptic transmission and an array of imaging strategies. Dr. Verstreken and his team have unraveled numerous aspects of how the synaptic vesicles from which a neurotransmitter is released are trafficked in presynaptic terminals, how this trafficking depends on energy supplied from mitochondria, and how these processes may be affected in neurodegenerative disease. Strikingly, he has identified vitamin K2, which is known for its role in bone formation and blood clotting, as a novel mitochondrial electron carrier molecule that is required to maintain high levels of mitochondrial activity and neurotransmitter release. These findings are important for understanding how synapses function and have potential relevance to devising therapies for Parkinson’s disease and related disorders. “In spite of his young age, Patrik has already made impressive contributions to neuroscience and has established himself as one of the most promising neuroscientists of his generation in Europe,” wrote Pietro De Camilli, M.D. (Eugene Higgins Professor of Cell Biology at Yale University, USA), in his letter of support for Dr. Verstreken. “His success as an independent investigator has been nothing short of spectacular.... He is also pursuing collaborations with industrial partners aimed at promoting a translation of his results into research with potential clinical relevance.

Affiliations and expertise

VIB Center for the Biology of Disease, KU Leuven, Center for Human Genetics, Laboratory of Neuronal Communication, Leuven, Belgium