Search results for: molecular-chaperones-in-health-and-disease

Molecular Chaperones in Health and Disease

Author : Matthias Gaestel
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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 in Health and Disease

Author : Matthias Gaestel
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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 in Health and Disease

Author : Matthias Gaestel
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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.

Cellular Trafficking of Cell Stress Proteins in Health and Disease

Author : Brian Henderson
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Since the beginning of the 21st Century there has been a rapid increase in our understanding of the cellular trafficking mechanisms of molecular chaperones in eukaryotes and in prokaryotes. In the former, molecular chaperone trafficking can occur between the various cellular compartments, with concomitant movement of other proteins. Such events can also result in the release of molecular chaperones from cells. In bacteria, molecular chaperones are involved in the trafficking of other proteins and are themselves released into the external milieu. The increasing appreciation of the role of molecular chaperones and Protein-Folding Catalysts in the interplay between bacteria and the cells of their hosts is now an important area of research for understanding the mechanisms of infectious diseases. This volume brings together experts in the biochemistry, cellular biology, immunology and molecular biology of molecular chaperones and Protein-Folding Catalysts with a focus on the mechanisms of cellular trafficking of these proteins and the role of these variegated trafficking mechanisms in both human and animal health and disease.

Cellular Trafficking of Cell Stress Proteins in Health and Disease

Author : Brian Henderson
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Since the beginning of the 21st Century there has been a rapid increase in our understanding of the cellular trafficking mechanisms of molecular chaperones in eukaryotes and in prokaryotes. In the former, molecular chaperone trafficking can occur between the various cellular compartments, with concomitant movement of other proteins. Such events can also result in the release of molecular chaperones from cells. In bacteria, molecular chaperones are involved in the trafficking of other proteins and are themselves released into the external milieu. The increasing appreciation of the role of molecular chaperones and Protein-Folding Catalysts in the interplay between bacteria and the cells of their hosts is now an important area of research for understanding the mechanisms of infectious diseases. This volume brings together experts in the biochemistry, cellular biology, immunology and molecular biology of molecular chaperones and Protein-Folding Catalysts with a focus on the mechanisms of cellular trafficking of these proteins and the role of these variegated trafficking mechanisms in both human and animal health and disease.

Molecular Chaperones

Author : Stuart K. Calderwood
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The proteome consists of a complex mixture of proteins each of which need to be folded correctly in order to function for the health of the organism, and many of these proteins require molecular chaperones to reach the correct conformation and, in some cases, to remain in a folded form. In Molecular Chaperones: Methods and Protocols, expert researchers address a wide variety of approaches to the study these mechanisms, featuring the workings of heat shock proteins and heat shock transcription factors, in vitro and in vivo. Written in the highly successful Methods in Molecular BiologyTM series format, chapters features introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Molecular Chaperones: Methods and Protocols serves as an ideal guide for all scientists who wish to pursue this vital biological action and its impact on human health and disease.

Inhibitors of Molecular Chaperones as Therapeutic Agents

Author : Timothy D. Machajewski
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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 Chaperonopathies

Author : Alberto J.L. Macario
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This Brief provides a concise review of chaperonopathies, i.e., diseases in which molecular chaperones play an etiologic-pathogenic role. Introductory chapters deal with the chaperoning system and chaperoning teams and networks, HSP-chaperone subpopulations, the locations and functions of chaperones, and chaperone genes in humans. Other chapters present the chaperonopathies in general, including their molecular features and mechanistic classification into by defect, excess, or mistake. Subsequent chapters discuss the chaperonopathies in more detail, focusing on their distinctive characteristics: primary or secondary; quantitative and/or qualitative; structural and hereditary or acquired; genetic polymorphisms; gene dysregulation; age-related; associated with cancer, chronic inflammatory conditions, and autoimmune diseases. The interconnections between the chaperoning and the immune systems in cancer development, chronic inflammation, autoimmunity, and ageing are outlined, which leads to a discussion on the future prospects of chaperonotherapy. The latter may consist of chaperone gene and protein replacement/supplementation in cases of deficiency and of gene or protein blocking when the chaperone actively promotes disease. The last chapter presents the extracellular chaperones and details on how the chaperone Hsp60 is secreted into the extracellular space and, thus, appears in the blood of cancer patients with potential to participate in carcinogenesis and chronic inflammation and autoimmunity. Chaperones as clinically useful biomarkers are mentioned when pertinent. Likewise, guidelines for clinical evaluation of chaperonopathies and for their histopathological and molecular identification are provided throughout. The book also provides extensive bibliography organized by chapter and topic with comments.

HSF1 and Molecular Chaperones in Biology and Cancer

Author : Marc Laurence Mendillo
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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.

Molecular Chaperones and Neurodegeneration

Author : Cintia Roodveldt
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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.