ETIOLOGY AND PATHOPHYSIOLOGY OF PARKINSON'S DISEASE Edited by Abdul Qayyum Rana Etiology and Pathophysiology of Parkinson's Disease Edited by Abdul Qayyum Rana Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Used under license from Shutterstock.com First published September, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Etiology and Pathophysiology of Parkinson's Disease, Edited by Abdul Qayyum Rana p. cm. 978-953-307-462-7 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Chapter 1 Etiology and Pathogenesis of Parkinson’s Disease 1 Taku Hatano and Nobutaka Hattori Chapter 2 Genetics of Parkinson Disease 15 Celeste Sassi Chapter 3 Parkin and Parkinson’s Disease 47 Shiam-Peng Tay, Grace G.Y. Lim, Calvin W.S. Yeo and Kah-Leong Lim Chapter 4 Modeling LRRK2 Parkinsonism 71 Kelly Hinkle and Heather Melrose Chapter 5 Alpha-Synuclein Interactions with Membranes 87 Katja Pirc and Nataša Poklar Ulrih Chapter 6 Alpha-Synuclein, Oxidative Stress and Autophagy Failure: Dangerous Liaisons in Dopaminergic Neurodegeneration 111 Giovanni Stefanoni, Gessica Sala, Lucio Tremolizzo, Laura Brighina and Carlo Ferrarese Chapter 7 Targeting α-Synuclein-Related Synaptic Pathology: Novel Clues for Parkinson’s Disease Therapy 137 Arianna Bellucci and PierFranco Spano Chapter 8 Effects of Alpha-Synuclein on Cellular Homeostasis 167 Kostas Vekrellis, Georgia Minakaki and Evangelia Emmanouilidou Chapter 9 Actions of GDNF on Midbrain Dopaminergic Neurons: The Signaling Pathway 193 Dianshuai Gao, Yi Liu, Shen Sun, Li Li and Ye Xiong VI Contents Chapter 10 The Hsp70 Chaperone System in Parkinson’s Disease 221 Adahir Labrador-Garrido, Carlos W. Bertoncini and Cintia Roodveldt Chapter 11 The Noradrenergic System is a Major Component in Parkinson’s Disease 247 Patricia Szot, Allyn Franklin and Murray A. Raskind Chapter 12 The Energy Crisis in Parkinson’s Disease: A Therapeutic Target 273 Mhamad Abou-Hamdan, Emilie Cornille, Michel Khrestchatisky, Max de Reggi and Bouchra Gharib Chapter 13 Analysis of Transcriptome Alterations in Parkinson’s Disease 293 Elena Filatova, Maria Shadrina, Petr Slominsky and Svetlana Limborska Chapter 14 Brain Mitochondrial Dysfunction and Complex I Syndrome in Parkinson´s Disease 317 Laura B. Valdez, Manuel J. Bandez, Ana Navarro and Alberto Boveris Chapter 15 Role of Microglia in Inflammatory Process in Parkinson’s Disease 329 Hirohide Sawada, Hiromi Suzuki, Kenji Ono, Kazuhiro Imamura, Toshiharu Nagatsu and Makoto Sawada Chapter 16 Oxidative DNA Damage and the Level of Biothiols, and L-Dopa Therapy in Parkinson’s Disease 349 Dorszewska Jolanta and Kozubski Wojciech Chapter 17 Inflammatory Responses and Regulation in Parkinson’s Disease 373 Lynda J. Peterson and Patrick M. Flood Chapter 18 Mathematical Models: Interactions Between Serotonin and Dopamine in Parkinson’s Disease 405 Janet Best, Grant Oakley, Michael Reed and H. Frederik Nijhout Chapter 19 Dopaminergic Control of the Neurotransmitter Release in the Subthalamic Nucleus: Implications for Parkinson’s Disease Treatment Strategies 421 Ben Ampe, Anissa El Arfani, Yvette Michotte and Sophie Sarre Chapter 20 Possible Contribution of the Basal Ganglia Brainstem System to the Pathogenesis of Parkinson’s Disease 433 Kaoru Takakusaki, Kazuhiro Obara and Toshikatsu Okumura Contents VII Chapter 21 Role of Lysosomal Enzymes in Parkinson’s Disease: Lesson from Gaucher’s Disease 459 Tommaso Beccari, Chiara Balducci, Silvia Paciotti, Emanuele Persichetti, Davide Chiasserini, Anna Castrioto, Nicola Tambasco, Aroldo Rossi, Paolo Calabresi, Veronica Pagliardini, Bruno Bembi and Lucilla Parnetti Chapter 22 Physiological and Biomechanical Analyses of Rigidity in Parkinson's Disease 485 Ruiping Xia Chapter 23 Mesothalamic Dopaminergic Activity: Implications in Sleep Alterations in Parkinson's Disease 507 Daniele Q. M. Madureira Chapter 24 Pathophysiology of Non-Dopaminergic Monoamine Systems in Parkinson's Disease: Implications for Mood Dysfunction 527 Nirmal Bhide and Christopher Bishop Preface Parkinson’s disease is a complex neurological condition which is quite disabling and interfering with one’s activities of daily life. The exact etiology of Parkinson’s disease remains unknown. Currently it is believed that Parkinson’s disease occurs due to interaction of environmental and genetic factors. Recently, there have been many significant developments in understanding the genetic mechanisms involved in Parkinson’s disease. This book not only provides a good review of the genetics of Parkinson’s disease but also gives a detail of other molecular pathways involved in the pathological process responsible for causation of Parkinson’s disease. A great focus has been given to pathophysiology of Parkinson’s disease, role of basal ganglia and other parts of brain involved in Parkinson’s disease. Every effort has been made to present correct and up to date information in this book, but medicine is a field with ongoing research and development, therefore readers may use other sources if the content of this book is found to be insufficient. Information presented in this book is considered generally accepted practice; however the authors, editor, and publisher are not responsible for any errors, omissions, or consequences from the application of this information. Dr. Abdul Qayyum Rana Parkinson's Clinic of Eastern Toronto & Movement Disorders Center, Toronto, Canada [...]... investigations of environmental and genetic factors of PD (Figure 1) 2 Etiology and Pathophysiology of Parkinson's Disease Fig 1 Although the etiology of Parkinson disease (PD) remains unknown, 5-10% of patients have clear familial etiology, which show a classical recessive or dominant Mendelian mode of inheritance On the other hand, MPTP or a combination of maneb and paraquat are environmental risk... Caamano-Isorna, F and Gestal-Otero, J J (2002) A metaanalysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease Ann Neurol, 52, 276-284 Etiology and Pathogenesis of Parkinson’s Disease 11 Ibanez, P., Bonnet, A M., Debarges, B., Lohmann, E., Tison, F., Pollak, P., Agid, Y., Durr, A and Brice, A (2004) Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. .. (2004) The new mutation, E46K, of alphasynuclein causes Parkinson and Lewy body dementia Ann Neurol, 55, 164-173 14 Etiology and Pathophysiology of Parkinson's Disease Zhang, N Y., Tang, Z and Liu, C W (2008) alpha-Synuclein protofibrils inhibit 26 S proteasome-mediated protein degradation: understanding the cytotoxicity of protein protofibrils in neurodegenerative disease pathogenesis J Biol Chem,... of Parkinson Disease 17 18 Etiology and Pathophysiology of Parkinson's Disease Genetics of Parkinson Disease 19 The classic approaches of linkage analysis and positional cloning have been very successful strategies to identify genes causing the autosomal-dominantly inherited diseases including the major forms of familial PD This strategy relies on the availability of large and clinically well-characterized... antagonists, and attenuated MPTP toxicity via A2A receptor blockade (Chen et al 2001) 2.4 Disease process and dual hit theory Braak and colleagues proposed neuropathological staging in PD They reported that the dorsal motor nucleus of the glossopharyngeal and vagal nerves and the anterior olfactory nucleus were initially affected, and subsequently the substantia nigra and locus coeruleus 4 Etiology and Pathophysiology. .. in the sporadic disease (MAPT, SNCA, HLA-DRB5, BST1, GAK and LRRK2) Finally a meta-analysis of the 5 previous GWAS discovered 5 new loci in association with the idiopatic disease (ACMSD, STK39, MCCC1/LAMP3, SYT11 and CCDC62/HIP1R) (International Parkinson Disease Genomics Consortium, 2011) 16 Etiology and Pathophysiology of Parkinson's Disease 2 Familial PD Familial PD is monogenic and caused by rare...1 Etiology and Pathogenesis of Parkinson’s Disease Taku Hatano and Nobutaka Hattori Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan 1 Introduction The pathological hallmarks of Parkinson’s disease (PD) are marked loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), which causes dopamine depletion in the striatum, and the presence of intracytoplasmic... of α-synuclein with proteins aggregating in other neurodegenerative diseases is coming increasingly into focus ‘Cross-seeding’ of α-synuclein and tau has been hypothesized by a recent study Interestingly this molecular mechanism may turn out to be the biological basis of the recently confirmed and refined association of MAPT haplotypes with PD and of an interaction of genetic variants in the SNCA and. .. fluctuations and dyskinesias Some show diurnal fluctuations, with symptoms becoming worse later in the day Dystonia at onset of the disease is common Parkin mutations turned out to be a common cause of parkinsonism 24 Etiology and Pathophysiology of Parkinson's Disease with early onset, particularly in individuals with evidence of recessive inheritance Nearly 50% of families from a population of sibling... with slower progression and a lower frequency of dementia and psychiatric complications In contrast to the finding that α-synuclein stains Lewy bodies and tau stains neurofibrillary tangles and grains, LRRK2 immunocytochemistry has so far failed to highlight any specific, 22 Etiology and Pathophysiology of Parkinson's Disease neurodegenerative lesion , and it is unclear how LRRK2 substitutions result . ETIOLOGY AND PATHOPHYSIOLOGY OF PARKINSON'S DISEASE Edited by Abdul Qayyum Rana Etiology and Pathophysiology of Parkinson's Disease Edited. for causation of Parkinson’s disease. A great focus has been given to pathophysiology of Parkinson’s disease, role of basal ganglia and other parts of brain involved in Parkinson’s disease. Every. pathway, and membrane trafficking (Hatano et al. 2009). In this chapter, we review the investigations of environmental and genetic factors of PD (Figure 1). Etiology and Pathophysiology of Parkinson's