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Oxidative Stress and Redox Signalling in Parkinson's Disease (Issues in Toxicology, 34) - Hardcover

 
9781782621881: Oxidative Stress and Redox Signalling in Parkinson's Disease (Issues in Toxicology, 34)
Hardcover
ISBN 10: 1782621881 ISBN 13: 9781782621881
Verlag: Royal Society of Chemistry, 2017

Inhaltsangabe

Parkinson's Disease is the second most common neurodegenerative disorder affecting millions of people worldwide. In order to find neuroprotective strategies, a clear understanding of the mechanisms involved in the dopaminergic death of cells that progresses the disease is needed. Oxidative stress can be defined as an imbalance between the production of reactive species and the ability to detoxify them and their intermediates or by-products. Oxidative damage to lipids, proteins, and DNA has been detected in autopsies from individuals with Parkinson’s Disease and so links can be made between oxidative stress and Parkinson’s Disease pathogenesis.
This book provides a thorough review of the mechanisms by which oxidative stress and redox signalling mediate Parkinson’s Disease. Opening chapters bring readers up to speed on basic knowledge regarding oxidative stress and redox signalling, Parkinson’s Disease, and neurodegeneration before the latest advances in this field are explored in detail. Topics covered in the following chapters include the role of mitochondria, dopamine metabolism, metal homeostasis, inflammation, DNA-damage and thiol-signalling. The role of genetics and gene-environment interactions are also explored before final chapters discuss the identification of potential biomarkers for diagnosis and disease progression and the future of redox/antioxidant based therapeutics.
Written by recognized experts in the field, this book will be a valuable source of information for postgraduate students and academics, clinicians, toxicologists and risk assessment groups. Importantly, it presents the current research that might later lead to redox or antioxidant – based therapeutics for Parkinson’s disease.  Parkinson's disease is the second most common neurodegenerative disorder affecting millions of people worldwide. In order to find neuroprotective strategies, the mechanisms of the disease need to be understood, and there have been links made between oxidative damage and Parkinson’s disease. This book provides a thorough review of the latest research developments regarding the mechanisms by which oxidative stress and redox signalling mediate Parkinson’s disease. It is designed to cover basic knowledge regarding oxidative stress and redox signalling, Parkinson’s disease, and neurodegeneration, while also exploring in detail the latest advancement in the research field. Topics covered will include dopamine metabolism, metal homeostasis and DNA-damage. The text will also discuss the current advance in the identification of potential biomarkers for diagnosis and disease progression and the future of antioxidant based therapeutics. Written by recognised experts in the field this book will be a great source of information for postgraduate students and academics, clinicians, toxicologists and risk assessment groups.

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Über die Autorin bzw. den Autor

Dr Franco is an Assistant Professor of Neuroscience at the Redox Biology Center, University of Nebraska-Lincoln. Prior to this position, he was post-doctoral fellow at the National Institute of Environmental Health Sciences, USA. His research interests include the role of oxidative stress and redox signaling in the regulation of cell death pathways, and in neuronal cell death associated with neurological disorders. He has been awarded the Layman Award and the SIGMA XI Outstanding Young Scientist Award.
Dr Doorn is an Associate Professor of Medicinal and Natural Products Chemistry at the University of Iowa, College of Pharmacy. Before this, he was a post-doctoral fellow at the University of Colorado Health Sciences Center, Depts. of Pharmaceutical Sciences and Pharmacology, USA. His postdoctoral work involved studying the role of lipid peroxidation products and protein carbonylation in alcoholic liver disease. Dr Doorn received his Ph.D. from the University of Michigan, School of Public Health, Toxicology Program.
Dr Rochet is an associate professor in the Department of Medicinal Chemistry and Molecular Pharmacology (College of Pharmacy) at Purdue University. Before his arrival at Purdue, Dr Rochet received his PhD degree at the University of Alberta in Biochemistry in 1998 and then worked as a post-doctoral fellow studying mechanisms of alpha-synuclein self-assembly in Parkinson’s disease in the laboratory of Dr. Peter Lansbury at Harvard Medical School. Dr.Rochet’s research group has a long-standing interest in Parkinson’s disease.

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Parkinson's Disease is the second most common neurodegenerative disorder affecting millions of people worldwide. In order to find neuroprotective strategies, a clear understanding of the mechanisms involved in the dopaminergic death of cells that progresses the disease is needed. Oxidative stress can be defined as an imbalance between the production of reactive species and the ability to detoxify them and their intermediates or by-products. Oxidative damage to lipids, proteins, and DNA has been detected in autopsies from individuals with Parkinson’s Disease and so links can be made between oxidative stress and Parkinson’s Disease pathogenesis.
This book provides a thorough review of the mechanisms by which oxidative stress and redox signalling mediate Parkinson’s Disease. Opening chapters bring readers up to speed on basic knowledge regarding oxidative stress and redox signalling, Parkinson’s Disease, and neurodegeneration before the latest advances in this field are explored in detail. Topics covered in the following chapters include the role of mitochondria, dopamine metabolism, metal homeostasis, inflammation, DNA-damage and thiol-signalling. The role of genetics and gene-environment interactions are also explored before final chapters discuss the identification of potential biomarkers for diagnosis and disease progression and the future of redox/antioxidant based therapeutics.
Written by recognized experts in the field, this book will be a valuable source of information for postgraduate students and academics, clinicians, toxicologists and risk assessment groups. Importantly, it presents the current research that might later lead to redox or antioxidant – based therapeutics for Parkinson’s disease. 

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Oxidative Stress and Redox Signalling in Parkinson's Disease

By Rodrigo Franco, Jonathan A. Doorn, Jean-Christophe Rochet

The Royal Society of Chemistry

Copyright © 2017 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-1-78262-188-1

Contents

Chapter 1 Etiology and Pathogenesis of Parkinson's Disease Briana R. de Miranda and J. Timothy Greenamyre, 1, 
Chapter 2 Oxidative Stress and Redox Signalling in the Parkinson's Disease Brain Pablo Hernandez-Franco, Annandurai Anandhan, Rachel M. Foguth and Rodrigo Franco, 27, 
Chapter 3 Mitochondrial Dysfunction in Parkinson's Disease Manisha Patel and Pallavi Bhuyan McElroy, 61, 
Chapter 4 Dopamine Metabolism and the Generation of a Reactive Aldehyde Josephine H. Schamp and Jonathan A. Doorn, 97, 
Chapter 5 Dopamine Oxidation and Parkinson's Disease Caitlyn W Barrett, Meghan L. Bucher and Teresa G. Hastings, 116, 
Chapter 6 Glutathione and Thiol Redox Signalling in Parkinson's Disease Michelle Smeyne and Richard Jay Smeyne, 144, 
Chapter 7 Neuroinflammation and Oxidative Stress in Models of Parkinson's Disease and Protein-Misfolding Disorders Ronald B. Tjalkens, Karin M. Streifel and Julie A. Moreno, 184, 
Chapter 8 Redox Signalling in Dopaminergic Cell Death and Survival Ajit Ray, Aditi Verma and Vijayalakshmi Ravindranath, 210, 
Chapter 9 Iron Metabolism in Parkinson's Disease Guofen Gao, Lin-Hao You and Yan-Zhong Chang, 255, 
Chapter 10 Protein Oxidation, Quality-Control Mechanisms and Parkinson's Disease Pablo Hernandez-Francoa, Annadurai Anandhan and Rodrigo Franco, 277, 
Chapter 11 At the Intersection Between Mitochondrial Dysfunction and Lysosomal Autophagy: Role of PD-Related Neurotoxins and Gene Products Josephat M. Asiago, Trevor B. Doyle, Vartika Mishra, Aurélie de Rus Jacquet and Jean-Christophe Rochet, 325, 
Chapter 12 Genes, Aging, and Parkinson's Disease Chiara Milanese and Pier G. Mastroberardino, 389, 
Chapter 13 Biomarkers of Oxidative Stress in Parkinson's Disease Emilio Fernández, 423, 
Chapter 14 Dietary Anti-, Pro-Oxidants in the Etiology of Parkinson's Disease Zeynep Sena Agim and Jason R. Cannon, 447, 
Subject Index, 505,


CHAPTER 1

Etiology and Pathogenesis of Parkinson's Disease

BRIANA R. DE MIRANDA AND J. TIMOTHY GREENAMYRE


1.1 Introduction

Parkinson's disease (PD) is the second most common neurodegenerative disorder (after Alzheimer's disease), and it is estimated that PD affects approximately 10 million individuals worldwide, though many cases may go undiagnosed. With the growth of aging populations, it is estimated that PD will nearly double in incidence over the next 25 years, representing a major social and economic burden to provide long-term treatment and care for those affected. This pressing concern has focused increased attention on the field of neurodegeneration, and while laboratory discoveries have begun translation into the clinic, one critical issue persists; the underlying causes of this progressive disorder remain, for the most part, unidentified. Inherited forms of PD strongly correspond to known genetic mutations in proteins involved with mitochondrial function, oxidative stress, and protein degradation pathways. However, inherited forms of PD only account for about 10% of PD cases, and sporadic PD has a much lower association with single gene mutations that are readily identified by specific protein dysfunction. The pathogenesis of both familial and idiopathic PD involves several components; the gross manifestations of the disorder, the underlying neuronal death and cellular pathology, the molecular mechanisms behind progressive degeneration, and the genetic or environmental dysregulation of proteins responsible for cellular dysfunction.

Currently, no curative or 'disease-modifying' therapy is available to slow or stop the inevitable and inexorable progression of PD. While symptomatic treatment options are available, as the disease progresses and medication doses rise, the tolerability of PD drugs may decrease and side effects often become problematic. In order to develop therapeutic strategies that prevent the progressive loss of dopamine neurons, a clear understanding of the mechanisms behind cell death in PD must be elucidated. Many putative pathological mechanisms in PD can be linked to common pathways that converge on the mitochondrial production of oxidative stress. Here, the pathogenesis of oxidative stress in PD is examined in the context of the cellular pathology observed in the disease.


1.2 Clinical Manifestations of Parkinson's Disease

The motor signs and symptoms of PD – bradykinesia, resting tremor, rigidity, and postural instability – together with the patient's history, are the primary means for identifying the disorder, and current guidelines require two of the four main signs of the disease to be present, typically presenting with asymmetrical onset. Most individuals are diagnosed over the age of 45, with only a small percentage (10%) of cases considered early-onset (under the age of 45). Accompanying these movement deficits are non-motor symptoms of PD, such as decreased GI motility, loss of olfactory function, sleep disorders, and cognitive or behavioral changes. Non-motor symptoms often occur prior to the onset of motor symptoms, though their presence alone has proven unreliable for detecting PD. Motor symptoms of PD occur when there is approximately 80% loss of striatal dopamine levels, indicating that significant cell death and damage has occurred prior to emergence of visible symptoms of the disease. This 'silent' period of pathogenesis is extremely problematic as it narrows the window for neuroprotective therapeutic intervention to the period after clinical diagnosis.

There is no definitive test for PD outside of the diagnostic criteria in the clinic and the response of a patient to levodopa (l-DOPA), which is the precursor of dopamine and the most efficacious symptomatic treatment for the disease. Unfortunately, maintenance with l-DOPA and dopamine receptor agonists has limitations. On the one hand, dopamine mimetics are useful at abating many of the symptoms in PD such as bradykinesia, rigidity, and tremor, while on the other hand they contribute to a host of iatrogenic symptoms, including dyskinesias, 'wearing off' effects, and hallucinations. In addition, treatment with dopamine agonists may exacerbate impulse control disorders, such as excessive gambling and reward-seeking behavior. There are also indications that dopamine-replacement therapy itself contributes to cellular toxicity, possibly enhancing the progressive loss of neurons associated with PD. Several small molecule therapies aimed at inhibiting the progression of PD have entered the pipeline for novel drug development, many of which are anti-inflammatory therapies targeted at limiting oxidative stress. It is critical to note, however, that no compound has been proven successful in Phase III clinical trials for this purpose, and the pursuit for new therapeutic strategies continues.


1.3 Neuropathology

Underlying many of the motor symptoms of PD is the selective loss of dopaminergic neurons of the substantia nigra pars compacta and their principal axon projections to the striatum. Degeneration of the nigrostriatal tract is considered the hallmark lesion of the disease; however, several other extranigral sites exhibit pathology: the locus coeruleus and subcoeruleus complex, reticular formation and raphe nuclei, dorsal nuclei of the Vagus, and nucleus basalis of Meynert may all display cell...

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Verlag
Royal Society of Chemistry
Erscheinungsdatum
2017
Sprache
Englisch
ISBN 10 
1782621881
ISBN 13 
9781782621881
Einband
Gebundene Ausgabe
Anzahl der Seiten
520
Herausgeber
Franco Rodrigo, Doorn Jonathan A., Rochet Jean-christophe
Kontakt zum Hersteller
Nicht verfügbar
Verantwortliche Person
Nicht verfügbar