Molecular Chaperones And Protein Folding As Therapeutic Targets In Parkinson S Disease And Other Synucleinopathies

Changes in protein metabolism are key to disease onset and progression in many neurodegenerative diseases. As a prime example, in Parkinson's disease, folding, post-translational modification and recycling of the synaptic protein alpha-synuclein are clearly altered, leading to a progressive accumulation of pathogenic protein species and the formation of intracellular inclusion bodies. Altered protein folding is one of the first steps of an increasingly understood cascade in which alpha-synuclein forms complex oligomers and finally distinct protein aggregates, termed Lewy bodies and Lewy neurites. In neurons, an elaborated network of chaperone and co-chaperone proteins is instrumental in mediating protein folding and re-folding. In addition to their direct influence on client proteins, chaperones interact with protein degradation pathways such as the ubiquitin-proteasome-system or autophagy in order to ensure the effective removal of irreversibly misfolded and potentially pathogenic proteins. Because of the vital role of proper protein folding for protein homeostasis, a growing number of studies have evaluated the contribution of chaperone proteins to neurodegeneration. We herein review our current understanding of the involvement of chaperones, co-chaperones and chaperone-mediated autophagy in synucleinopathies with a focus on the Hsp90 and Hsp70 chaperone system. We discuss genetic and pathological studies in Parkinson's disease as well as experimental studies in models of synucleinopathies that explore molecular chaperones and protein degradation pathways as a novel therapeutic target. To this end, we examine the capacity of chaperones to prevent or modulate neurodegeneration and summarize the current progress in models of Parkinson's disease and related neurodegenerative disorders.

Protein misfolding and amyloid formation is an underlying pathological hallmark in a number of prevalent diseases of protein aggregation, including Parkinson's disease (PD), Alzheimer's disease and Type 2 diabetes. Most importantly, the severity of these diseases appears to correlate with the degree of the deposition of amyloid aggregates. The misfolding of -synuclein, a protein involved in PD, followed by its aggregation has been shown to be highly cytotoxic and to play a key role in the death of neurons. Thus, the modulation of the aggregation process, promoting the proper folding of -synuclein, may be considered as an attractive avenue for a therapeutic intervention. Indeed, molecular chaperones have been shown to assist in the maintenance of a functional proteome in vivo and to prevent protein misfolding, aggregation and amyloid formation."

Disease-Modifying Targets in Neurodegenerative Disorders: Paving the Way for Disease-Modifying Therapies examines specific neurodegenerative disorders in comprehensive chapters written by experts in the respective fields. Each chapter contains a summary of the disease management field, subsequently elaborating on the molecular mechanisms and promising new targets for disease-modifying therapies. This overview is ideal for neuroscientists, biomedical researchers, medical doctors, and caregivers, not only providing readers with a summary of the way patients are treated today, but also offering a glance at the future of neurodegenerative disorder treatment. Provides a comprehensive overview of how key proteins in neurodegenerative disorders can be used as targets to modify disease progress Summarizes how patients are treated today, providing a glance at future disease management Includes intelligible and informative information that is perfect for non-specialists, medical practitioners, and scientists Written and peer reviewed by outstanding scientists in their respective fields

The book HSP70 in Human Diseases and Disorders provides the most comprehensive review on contemporary knowledge on the role of HSP70 family - one of the most studied HSP - in human diseases and disorders. Using an integrative approach to expand our current understanding of HSP70 functions, the contributors provide a synopsis of novel mechanisms by which HSP70 is involved in the regulation of human diseases and disorders. Key basic and clinical research laboratories from major universities and academic medical hospitals around the world contribute chapters that review present research activity and importantly project the field into the future. The book is a must read for medical students and residents, clinical and basic science researchers, postdoctoral fellows and graduate students in the fields of Medicine, Physiology, Clinical Trials, Biotechnology, Molecular Medicine and Pathology.

The 2nd World Congress on Genetics, Geriatrics and Neurodegenerative Disease Research (GeNeDis 2016), will focus on recent advances in geriatrics and neurodegeneration, ranging from basic science to clinical and pharmaceutical developments and will provide an international focum for the latest scientific discoveries, medical practices, and care initiatives. Advances information technologies will be discussed along with their implications for various research, implementation, and policy concerns. In addition, the conference will address European and global issues in the funding of long-term care and medico-social policies regarding elderly people. GeNeDis 2016 takes place in Sparta, Greece, 20-23 October, 2016. This volume focuses on thesessions that address neurodegenerative diseases.

This informative book discusses the latest research on the risk factors and therapeutics in dementia. WHO calls dementia a public health priority. Dementia manifests as a group of symptoms associated with decline in memory or other thinking skills and is severe enough to reduce a person's ability to perform everyday activities. It occurs frequently among elderly people, but it is not necessarily part of the normal aging process. The book has been divided into two broad sections. The first section reviews the risk factors involved in developing dementia, including various medical conditions, lifestyle choices, as well as genetics. The latter section describes various therapeutic interventions in dementia. Although there is no known cure for dementia, this book underlines the current treatment strategies that could momentarily reduce the symptoms and improve the quality of life of the patients. This book highlights the global effort to find better ways to halt the progression of dementia and develop novel therapeutic strategies. The book would be an interesting read for advanced graduate students and researchers working in the field of neuroscience, genetics, and medicine. It will generate good interest to neurologists, psychiatrists, geriatricians, cardiologists, internal medicine practitioners, epidemiologist, and public health workers.

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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.