Molecular Chaperones in Health and Disease


Book Description

Molecular chaperones are involved in a wide variety of essential cellular processes in living cells. A subset of molecular chaperones have been initially described as heat shock proteins protecting cells from stress damage by keeping cellular proteins in a folding competent state and preventing them from irreversible aggregation. Later it became obvious that molecular chaperones are also expressed constitutively in the cell and are involved in complex processes such as protein synthesis, intracellular protein transport, post-translational modification and secretion of proteins as well as receptor signalling. Hence, it is not surprising that molecular chaperones are implicated in the pathogenesis of many relevant diseases and could be regarded as potential pharmacological targets. Starting with the analysis of the mode of action of chaperones at the molecular, cellular and organismic level, this book will then describe specific aspects where modulation of chaperone action could be of pharmacological and therapeutic interest.




Quality Control of Cellular Protein in Neurodegenerative Disorders


Book Description

Protein misfolding and aggregation are hallmarks of several neurodegenerative proteinopathies. Though multiple factors like aging, oxidative stress, mitochondrial dysfunction, proteotoxic insults, genetic inconsistency, etc. are responsible for the dysfunction of the neuronal protein quality control system, targeting protein quality control has become an auspicious approach to halt the propagation of neurodegeneration. Quality Control of Cellular Protein in Neurodegenerative Disorders provides diverse aspects exploring the role of the protein quality control in neurodegenerative disorders and potential therapeutic strategies to combat the development and propagation of neurodegeneration. Featuring coverage on a broad range of topics such as molecular chaperones, protein misfolding, and stress signaling, this book is ideally designed for neurobiologists, neuropsychologists, neurophysiologists, medical professionals, neuropathologists, researchers, academicians, students, and practitioners engaged in studies of the protein quality control system in neuronal cells.




HSF1 and Molecular Chaperones in Biology and Cancer


Book Description

Protein homeostasis, or “Proteostasis”, lies at the heart of human health and disease. From the folding of single polypeptide chains into functional proteins, to the regulation of intracellular signaling pathways, to the secreted signals that coordinate cells in tissues and throughout the body, the proteostasis network operates to support cell health and physiological fitness. However, cancer cells also hijack the proteostasis network and many of these same processes to sustain the growth and spread of tumors. The chapters in this book are written by world experts in the many facets of the proteostasis network. They describe cutting-edge insights into the structure and function of the major chaperone and degradation systems in healthy cells and how these systems are co-opted in cancer cells and the cells of the tumor microenvironment. The chapters also cover therapeutic interventions such as the FDA-approved proteasome inhibitors Velcade and Krypolis as well as other therapies currently under clinical investigation to disarm the ability of the proteostasis network to support malignancy. This compendium is the first of its kind and aims to serve as a reference manual for active investigators and a primer for newcomers to the field. This book is dedicated to the memory of Susan Lindquist, a pioneer of the proteostasis field and a champion of the power of basic scientific inquiry to unlock the mechanisms of human disease. The chapter “Reflections and Outlook on Targeting HSP90, HSP70 and HSF1 in Cancer: A Personal Perspective” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.




GeNeDis 2016


Book Description

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 the sessions that address geriatrics.




Molecular Chaperones in Health and Disease


Book Description

Molecular chaperones are involved in a wide variety of essential cellular processes in living cells. A subset of molecular chaperones have been initially described as heat shock proteins protecting cells from stress damage by keeping cellular proteins in a folding competent state and preventing them from irreversible aggregation. Later it became obvious that molecular chaperones are also expressed constitutively in the cell and are involved in complex processes such as protein synthesis, intracellular protein transport, post-translational modification and secretion of proteins as well as receptor signalling. Hence, it is not surprising that molecular chaperones are implicated in the pathogenesis of many relevant diseases and could be regarded as potential pharmacological targets. Starting with the analysis of the mode of action of chaperones at the molecular, cellular and organismic level, this book will then describe specific aspects where modulation of chaperone action could be of pharmacological and therapeutic interest.




Molecular Chaperones and Neurodegeneration


Book Description

Molecular chaperones or heat-shock proteins (HSPs) play essential roles in safeguarding structural stability and preventing misfolding and aggregation of proteins, and maintaining the proteome functionality in the cell. For over two decades until the present time, new functions have been discovered and several molecular mechanisms have been elucidated for many chaperones, while the field is being continuously challenged by new open questions. Probably as a consequence of the increasing research on the molecular bases of neurodegenerative diseases, and the realisation that many such disorders are linked to protein misfolding processes, unleashing the roles and mechanisms of chaperones in the context of neurodegeneration has become a prime scientific goal. This e-book contains a diversity of reviews, perspective and original research articles highlighting the importance and potential of this emerging subject.




Molecular Chaperones in Human Disorders


Book Description

Molecular Chaperones in Human Disorders, Volume 114 in the Advances in Protein Chemistry and Structural Biology series, provides an overview of current developments in mechanisms underlying DNA repair and their involvement in maintaining chromatin repair, the balance between chromosomal repair pathways, tumorigenesis, immune signaling and infection-induced inflammation. Chapters in this new release cover Functional principles and regulation of molecular chaperones, Chaperones and retinal disorders, Protein misfolding and degradation in genetic diseases, Chaperone dysfunction in hereditary myopathic diseases, Diseases caused by functional disorder of molecular chaperones residing in the endoplasmic reticulum, and many other timely topics. - Describes advances in our understanding on DNA repair mechanisms and the involvement of their dysregulation in promoting diseases - Provides an ideal resource for a very wide audience of specialists, researchers and students - Contains timely chapters written by well-renown authorities in their field - Presents information that is well supported by a number of high quality illustrations, figures and tables




The Molecular Chaperones Interaction Networks in Protein Folding and Degradation


Book Description

Molecular chaperones are a fundamental group of proteins that have been identified only relatively recently. They are key components of a protein quality machinery in the cell which insures that the folding process of any newly-synthesized polypeptide chain results in the formation of a properly folded protein and that the folded protein is maintained in an active conformation throughout its functional lifetime. Molecular chaperones have been shown to play essential roles in cell viability under both normal and stress conditions. Chaperones can also assist in the unfolding and degradation of misfolded proteins and in disaggregating preformed protein aggregates. Chaperones are also involved in other cellular functions including protein translocation across membranes, vesicle fusion events, and protein secretion. In recent years, tremendous advances have been made in our understanding of the biology, biochemistry, and biophysics of function of molecular chaperones. In addition, recent technical developments in the fields of proteomics and genomics allowed us to obtain a global view of chaperone interaction networks. Finally, there is now a growing interest in the role of molecular chaperones in diseases. This book will provide a comprehensive analysis of the structure and function of the diverse systems of molecular chaperones and their role in cell stress responses and in diseases from a global network perspective. ​




Inhibitors of Molecular Chaperones as Therapeutic Agents


Book Description

This book aims to provide a comprehensive examination of the field of molecular chaperone inhibition and its application to pharmaceutical research. With several small molecule inhibitors in oncology clinical development, there is clearly intense interest in the chaperones as a molecular target. Filling a significant gap in the market by providing a detailed comparison of discovery programs across the industry, this text will find broad interest among researchers in the field of molecular chaperone pharmaceutical research, oncology research, and medicinal chemistry. Arranged into three main sections the book covers structure and function, small molecule inhibitors and concludes with a section discussing clinical perspectives. With specific chapters covering the discovery of key molecules such as, BIIB028, STA-9090, Serenex Hsp90 inhibitor, NVP-AUY922 and NVP-HSP990, this comprehensive text will be an essential treatise for researchers working in academia and industry.




The multitasking molecular chaperone Hsp60


Book Description

The Multitasking Molecular Chaperone Hsp60: Structure, Function, and Impact on Health and Disease provides an overview of this key component of the Chaperone System (CS). The book covers various areas of medicine in which Hsp60 chaperonopathies have been identified. Various chapters discuss the Hsp60 structure, localization, functions, and participation in disease mechanisms both genetic and acquired, focusing on humans but also presenting data obtained from pro- and eukaryotic experimental models. The main goal is to provide information accessible to all healthcare professionals in a way that can be understood by nonspecialists and that would stimulate clinical and pathological detection of Hsp60 chaperonopathies.Molecular mechanisms are briefly described with the purpose of illuminating roads toward accurate diagnosis, treatment, and patient monitoring. Consequently, the possibility of developing/applying chaperonotherapy centered on Hsp60, as a therapeutic tool or target, is analyzed in many sections of this book, across a variety of medical specialties. Over the last several years, the importance of the CS as a physiological system has been brought to prominence and its roles in health and disease made clear. The molecular chaperones, including Hsp60, are the key components of the CS that are typically cytoprotective, but they can also be etiopathogenic factors, causing diseases named chaperonopathies. - Discusses strategies for diagnosis, patient monitoring, and treatment of disorders in which Hsp60 plays a role and can be used as biomarker and therapeutic target or agent - Explains the fundamental biophysics, genetics, physiology, and pathogenicity of Hsp60 - Explores the mechanisms involving Hsp60 abnormalities causing disease, including carcinogenesis, inflammation, autoimmunity, and neurodegenerative disorders