Endoplasmic Reticulum Stress in Health and Disease


Book Description

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ‘ER stress’. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.




The Unfolded Protein Response


Book Description

This volume is divided in six section covering the most experimental approaches involved in the study of the unfolded protein response (UPR) pathway. Chapters detail determination of unfolded protein levels, methods to study UPR signal transmission, analysing the outcomes of the UPR pathway activation, UPR studies in mammalian models, UPR in alternative models, and UPR and disease. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, The Unfolded Protein Response: Methods and Protocols aims to describe key methods and approaches used in the study of the UPR pathway and its complex cellular implications. Chapter 6 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.




The Unfolded Protein Response in Cancer


Book Description

This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation. Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.




Preimplantation Embryo Development


Book Description

This volume contains the Proceedings of the Serono Symposium on Pre implantation Embryo Development, held in Newton, Massachusetts, in 1991. The idea for the symposium grew out of the 1989 Serono Symposium on Fertilization in Mammals* at which preimplantation development was the predominant suggestion for a follow-up topic. This was indeed a timely subject in view of the recent resurgence of interest in this funda mental phase of embryogenesis and its relevance to basic research and applied fertility studies in humans, food-producing animals, and endangered species. The symposium brought together speakers from a broad range of disciplines in order to focus on key regulatory mechanisms in embryo development, using a wide variety of animal models, and on representative topics in human preimplantation embryogenesis. The culmination of preimplantation development is a blastocyst con taining the first differentiated embryonic tissues and capable of initiating and sustaining pregnancy. The central objective of the symposium was to throw light on the regulation of cellular and molecular events underlying blastocyst formation. It was particularly appropriate that the date of the symposium marked the 20th anniversary of the publication of the classic volume Biology of the Blastocyst, the proceedings of an international workshop held in 1970. This book, which summarized most of the information then available on this topic in mammals, was edited by the pioneer in blastocyst research, Dr. Richard B1andau, who was the guest speaker at the symposium.




Cellular Biology of the Endoplasmic Reticulum


Book Description

This book provides a comprehensive overview of the biology of the endoplasmic reticulum (ER) and the associated ER proteins, it discusses their structure, function and signaling mechanisms in the cell and their role in disease. This book also offers insights into the practical aspects of research and demonstrates the use of non-mammalian models to study the structure and function of the ER. Written by leading experts in the field, the book enables readers to gain a thorough understanding of current ER biology. It is intended for scientists and clinical researchers working on the endoplasmic reticulum in all its various roles and facets in health and disease.




Endothelium and Cardiovascular Diseases


Book Description

Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes provides an in-depth examination of the role of endothelium and endothelial dysfunction in normal vascular function, and in a broad spectrum of clinical syndromes, from atherosclerosis, to cognitive disturbances and eclampsia. The endothelium is a major participant in the pathophysiology of diseases, such as atherosclerosis, diabetes and hypertension, and these entities are responsible for the largest part of cardiovascular mortality and morbidly. Over the last decade major new discoveries and concepts involving the endothelium have come to light. This important reference collects this data in an easy to reference resource. Written by known experts, and covering all aspects of endothelial function in health and disease, this reference represents an assembly of recent knowledge that is essential to both basic investigators and clinicians. - Provides a complete overview of endothelial function in health and diseases, along with an assessment of new information - Includes coverage of groundbreaking areas, including the artificial LDL particle, the development of a new anti-erectile dysfunction agent, a vaccine for atherosclerosis, coronary calcification associated with red wine, and the interplay of endoplasmic reticulum/oxidative stress - Explores the genetic features of endothelium and the interaction between basic knowledge and clinical syndromes




Extracellular Matrix Degradation


Book Description

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.




Handbook of Arsenic Toxicology


Book Description

Throughout history, arsenic has been used as an effective and lethal poison. Today, arsenic continues to present a real threat to human health all over the world, as it contaminates groundwater and food supplies. Handbook of Arsenic Toxicology presents the latest findings on arsenic, its chemistry, its sources and its acute and chronic effects on the environment and human health. The book takes readings systematically through the target organs, before detailing current preventative and counter measures. This reference enables readers to effectively assess the risks related to arsenic, and provide a comprehensive look at arsenic exposure, toxicity and toxicity prevention. - Brings together current findings on the effects of arsenic on the environment and human health - Includes state-of-the-art techniques in arsenic toxicokinetics, speciation and molecular mechanisms - Provides all the information needed for effective risk assessment, prevention and countermeasure




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.




Cardiac Left Ventricular Hypertrophy


Book Description

Left ventricular hypertrophy (LVH) is usually considered to be a compen satory adjustment of heart muscle to an inreased work load. LVH develops in the course of valvular or congenital heart disease, or when part of the myocardium is damaged by long-standing ischemia or infarction. In the hypertrophied heart the muscle fibers increase in size, not in number. The fibers are found to contain a larger number of myofibrils and the cell organelles are larger. From epidemiologic studies it is known that even mild LVH is associated with myocardial ischemia, ventricular arrhythmias, and sudden cardiac death. Most cases of LVH show focal degenerative tissue changes including cellular atrophy, myofibrillar disorganization, interstitial fibrosis, and loss of intracellular connections. Myocardial dysfunction develops and, unlike the functional adaptive changes found in pure hypertrophy, is not reversible by surgical treatment of the valvular heart disease or medical correction of hypertension. Interstitial fibrosis, intracellular changes of musc Ie cells, and loss of contract ile tissue lead to poor mechanical function and undoubtedly increase the risk of ischemia, arrhythmias, or sudden death, a well-recognized problem in patients with a variety of heart diseases. Even When successfully treated, the patients may remain at risk if the compensatory hypertrophy is not fully reversed. Epidemiologic studies conducted in the Framingham population in the early 1950' s demonstrated LVH according to electrocardiographic criteria in 1. 5% of the population; 2% of the population had LVH according to chest X-ray criteria.