Proteases occur naturally in all organisms. They are enzymes that are involved in many physiological reactions such as digestion of food and blood clotting. This volume reviews their role in health and disease and presents the latest research and developments. Discusses new discoveries, approaches, and ideas Contributions from leading scholars and industry experts Reference guide for researchers involved in molecular biology and related fields

In view of rapidly growing research in the deregulation of proteases and their impact in human health and diseases, this book will highlight existing and emerging research in this exciting area. In-depth critical state-of-the-art reviews will be written by established investigators on proteases dysfunctions associated with pathogenesis of different diseases that are known to occur due to deregulation of proteolytic systems. Multidisciplinary approaches demonstrating biochemical and signal transduction mechanisms associated with deregulation of proteases leading to manifestation of the diseases will be discussed. The book highlights the roles of both intracellular and extracellular proteases in health and disease.

We are pleased to present to our readers the Proceedings of the International Symposium "Proteases: Potential Role in Health and Disease" which was held in WUrzburg (FRG) during October 17-20, 1982. The topics discussed included those dealing with the physi ology and pathophysiology of proteases and their inhibitors, the interactions of proteases and hormones, the kallikrein-kinin system, complement and the coagulation system, the function of proteases in the kidney and the intestinal tract as well as the role of proteases in lung diseases, pancreatitis, arthritis and hypercatabolic states (multiple trauma, septicemia, acute renal failure). The papers presented answered many questions, but raised many more concerning the significance of proteases and their inhibitors in clinical medicine. It was unfortunately impossible in this volume to in clude the extended, lively and extremely stimulating discussions which were enjoyed by the participants during the conference. The meeting has provided a unique framework for close inter action between scientists from various disciplines, including bio chemistry, physiology, surgery, anaesthesiology, endocrinology, hematology, pulmonology and nephrology. We would like to express our thanks and appreciation for all those who have stimulated, encouraged and supported us to hold this symposium in WUrzburg. This endeavor could not have been possible without the generous financial support of the Paul-Martini Foundation (Mainz), Bayer AG (Leverkusen), Beiersdorf AG (Hamburg).

In recent years, powered by evolving technologies and experimental design, studies have better illuminated the regulating role of proteolytic enzymes across human development and pathologies. Proteolytic Signaling in Health and Disease provides an in-depth discussion of fundamental physiological and developmental processes regulated by proteases, from protein turnover and autophagy to antigen processing and presentation and major histocompatibility complex (MHC) molecules. Moving on from basic biology, international chapter authors examine a range of pathological conditions associated with proteolysis, including inflammation, wound healing, and cancer. Later chapters discuss the newly discovered network of connected events among proteases (and their inhibitors), the so-called ‘protease web’, and how best to study it. This book also empowers new research with up-to-date analytical methods and step-by-step protocols for studying proteolytic signaling events. Examines biological events triggered by proteolytic enzyme activity across human development and pathologies Discusses the role of proteolytic signaling in inflammation, wound healing, and cancer, among other disease types Features methods and protocols supporting further study of proteolytic signaling events Includes chapter contributions from international leaders in the field

This book bridges the gap between fundamental research and biomedical and pharmacological applications on proteases. It represents a comprehensive overview of the multifaceted field of proteases in cellular environment and highlights the recently elucidated functions of complex proteolytic systems in different diseases. Several established investigators have elucidated the crucial role of proteases in biological processes, including how proteolytic function and regulation can be combined to develop new strategies of therapeutic interventions. Proteases form one of the largest and most diverse families of enzymes known. It is now clear that proteases are involved in every aspect of life functions of an organism. Under physiological conditions, proteases are regulated by their endogenous inhibitors; however, when the activity of proteases is not regulated appropriately, disease processes can result in. So, there is absolute need for a stringent control of proteolytic activities in cells and tissues. Dysregulation of proteases may cause derangement of cellular signalling network resulting in different pathophysiological conditions such as vascular remodelling, atherosclerotic plaque progression, ulcer and rheumatoid arthritis, Alzheimer disease, cancer metastasis, tumor progression and inflammation. Additionally, many infective microorganisms require proteases for replication or use proteases as virulence factors, which have facilitated the development of protease-targeted therapies for a variety of parasitic diseases.

Using a multidisciplinary approach, this book describes the biochemical mechanisms associated with dysregulation of proteases and the resulting pathophysiological consequences. It highlights the role and regulation of different types of proteases as well as their synthetic and endogenous inhibitors. The role of proteases was initially thought to be limited to general metabolic digestion. However, we now know that the role of protein breakdown is much more complex, and proteases have multiple functions: they are coupled to turnover and can affect protein composition, function and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions, including activating and inactivating enzymes, modulating membrane function, altering receptor channel properties, affecting transcription and cell cycles and forming active peptides. The ubiquity of proteases in nature makes them an important target for drug development. This in-depth, comprehensive is a valuable resource for researchers involved in identifying new targets for drug development. With its multidisciplinary scope, it bridges the gap between fundamental and translational research in the biomedical and pharmaceutical industries, making it thought-provoking reading for scientists in the field.

It is now well known that proteases are found everywhere, in viruses and bacteria as well as in all human, animal and plant cells, and play a role in a variety of biological functions ranging from digestion, fertilization, development to senescence and death. Under physiological conditions the ability of proteases is regulated by endogenous inhibitors. However, when the activity of proteases is not regulated appropriately, disease processes can result, as seen in Alzheimer’s disease, cancer metastasis and tumor progression, inflammation and atherosclerosis. Thus it is evident that there is an absolute need for a tighter control of proteolytic activities in different cells and tissues. Aimed at graduate students and researchers with an interest in cellular proteolytic events, Role of Proteases in Cellular Dysfunctions is the second book on Proteases in this series. The book consists of three parts in specified topics based on current literatures for a better understanding for the readers with respect to their subject-wise interests. The first section of this book covers a brief idea about the neuronal disorders and the involvement of proteases such as calpains, caspases and matrix metalloproteases (MMPs). The second section covers the deadly disease cancer and its relation to ubiquitin-proteasome system, MMPs and serine proteases. The last section is about the role of proteases such as calpains, MMPs and serine protease as well as urokinase type plasminogen activator receptor (uPAR) in causing cardiovascular defects.

This book provides an account of the recent advances in our understanding of the role of proteases under physiological and pathological conditions. It reviews the contributions that have been made in the fields of biochemistry, molecular biology, medicine, agriculture and ecology. In addition there is an account of the growing number of practical applications in biotechnology, reflecting the fact that peptidases are major targets for medical and agricultural purposes. The book shows how the numerous protease structures are essential for drug design. The contributions place special emphasis on cysteine, aspartic and metalloproteases and their role in physiological and certain pathological states. Another focus is the classification and nomenclature of peptidases and a review of those proteases currently under the most intensive investigation. The book provides an informative introduction for teachers and newcomers to the field, such as graduate students, while providing a valuable source of material and ideas for the academic and industrial researcher in areas including biochemistry, medicine, agriculture and biotechnology.

Proteolysis is an irreversible posttranslational modification affecting each and every protein from its biosynthesis to its degradation. Limited proteolysis regulates targeting and activity throughout the lifetime of proteins. Balancing proteolysis is therefore crucial for physiological homeostasis. Control mechanisms include proteolytic maturation of zymogens resulting in active proteases and the shut down of proteolysis by counteracting endogenous protease inhibitors. Beyond the protein level, proteolytic enzymes are involved in key decisions during development that determine life and death – from single cells to adult individuals. In particular, we are becoming aware of the subtle role that proteases play in signaling events within proteolysis networks, in which the enzymes act synergistically and form alliances in a web-like fashion. Proteases come in different flavors. At least five families of mechanistically distinct enzymes and even more inhibitor families are known to date, many family members are still to be studied in detail. We have learned a lot about the diversity of the about 600 proteases in the human genome and begin to understand their physiological roles in the degradome. However, there are still many open questions regarding their actions in pathophysiology. It is in this area where the development of small molecule inhibitors as therapeutic agents is extremely promising. Approaching proteolysis as the most important, irreversible post-translational protein modification essentially requires an integrated effort of complementary research disciplines. In fact, proteolytic enzymes seem as diverse as the scientists working with these intriguing proteins. This book reflects the efforts of many in this exciting field of research where team and network formations are essential to move ahead.