Proteases In Human Diseases

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.

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

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.

Serine proteases play significant roles in healh and human disease. Abnormal expression and activities of serine proteases have been linked to the pathogenesis of many diseases. The book presents correlation between serine proteases and human diseases. It helps the reader understand classification, catalytic mechanism and types of serine proteases and their role in human disease pathogenesis at mechanistic level. The chapters explain the role of serine proteases in various diseases including respiratory disorders and cancer. It also covers the therapeutic importance of serine proteases as drug target and explains the mechanistic insights of serine proteases inhibitors. Serine protease are known to play crucial role in biological processes but disturbance in their equilibrium can result in serious health conditions. To maintain homeostasis, serine protease inhibitors come in action and inhibit proteases. Several serine protease inhibitors have been identified and many more are being designed as novel compounds for inhibitions of proteases that provide management of comorbidities. Therefore, this book will serve as a useful reference for students and researchers to understand physiological role of serine proteases and their association with initiation and progression of human diseases. It will also help to develop some strategies to develop serine proteases inhibitors as drug target of serine proteases at cellular and molecular level.

Viral Proteases and Their Inhibitors provides a thorough examination of viral proteases from their molecular components, to therapeutic applications. As information on three dimensional structures and biological functions of these viral proteases become known, unexpected protein folds and unique mechanisms of proteolysis are realized. This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. Users will find descriptions of each virus that detail the structure and function of viral proteases, discuss the design and development of inhibitors, and analyze the structure-activity relationships of inhibitors. This book is ideal biochemists, virologists and those working on antiviral agents. Provides comprehensive, state-of-the-art coverage of virus infections, the virus lifecycle, and mechanisms of protease inhibition Analyzes structure-activity relationships of inhibitors of each viral protease Presents an in-depth view of the structure and function of viral proteases

Abstract: Mitochondria contain more than 1000 different proteins, including several proteolytic enzymes. These mitochondrial proteases form a complex system that performs limited and terminal proteolysis to build the mitochondrial proteome, maintain, and control its functions or degrade mitochondrial proteins and peptides. During protein biogenesis, presequence proteases cleave and degrade mitochondrial targeting signals to obtain mature functional proteins. Processing by proteases also exerts a regulatory role in modulation of mitochondrial functions and quality control enzymes degrade misfolded, aged, or superfluous proteins. Depending on their different functions and substrates, defects in mitochondrial proteases can affect the majority of the mitochondrial proteome or only a single protein. Consequently, mutations in mitochondrial proteases have been linked to several human diseases. This review gives an overview of the components and functions of the mitochondrial proteolytic machinery and highlights the pathological consequences of dysfunctional mitochondrial protein processing and turnover

The 8th volume in the Proteases in Biology and Disease series focuses on the role of proteases in virus function and their potential as anti-viral targets. Viral infections are still difficult to threat and some remained life-threatening diseases in spite of antiviral drug research over decades. Proteases are still regarded as an Achilles’ heel of the pathogens and, thus, protease inhibitors may help to handle the known and the emerging viral threads. The book discusses viral proteases of the most important pathogenic viruses, responsible for severe diseases: AIDS, SARS, Hepatitis, Cytomegalovirus, T-cell lymphotropic virus, Picornavirus. This book focuses specifically on the viral proteases, crucial prerequisites for viral entry into cells and viral replication. Viral proteases represent an important pharmaceutical target. The current stage of protease inhibitor development and therapy are summarised and discussed by experts in the field. This volume represents a timely and valuable continuation of the Proteases in Biology and Disease series. The reader will learn the potential for proteases as targets for effective anti-virals. This book will be a valuable source of information on viral proteases and provoke further research in this important field.

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).