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Serpins constitute a superfamily of proteins that possess a unique tertiary structure and mechanism of proteinase inhibition. In humans, serpins constitute 10% of the plasma proteins and are best known as critical regulators of both the thrombotic and fibrinolytic systems. Serpins also participate in the regulation of the complement cascade, angiogenesis, tumor metastasis, apoptosis and innate immunity. Considering the importance of these molecules in regulating proteolytic cascades, it is not surprising to find that loss- and gain-of-function mutations result in significant human diseases.Massive thrombosis or bleeding, hereditary angioedema, Alzheimer's disease, diabetic angiopathy and tumor invasion are some of the human diseases associated with serpins. In addition, mutations that alter serpin conformations (the serpinopathies) lead to lung disease, cirrhosis and a form of familial dementia. The goal of this text is to present the current knowledge on the molecular and cellular basis of serpins and their diseases.
Serpins constitute a superfamily of proteins that possess a unique tertiary structure and mechanism of proteinase inhibition. In humans, serpins constitute 10% of the plasma proteins and are best known as critical regulators of both the thrombotic and fibrinolytic systems. Serpins also participate in the regulation of the complement cascade, angiogenesis, tumor metastasis, apoptosis and innate immunity. Considering the importance of these molecules in regulating proteolytic cascades, it is not surprising to find that loss- and gain-of-function mutations result in significant human diseases.Massive thrombosis or bleeding, hereditary angioedema, Alzheimer's disease, diabetic angiopathy and tumor invasion are some of the human diseases associated with serpins. In addition, mutations that alter serpin conformations (the serpinopathies) lead to lung disease, cirrhosis and a form of familial dementia. The goal of this text is to present the current knowledge on the molecular and cellular basis of serpins and their diseases.
International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment. MET and RON are activated by their particular ligands, the growth factors HGF and MSP, respectively. Blocking MET and RON kinase activation and downstream signaling is a promising therapeutic strategy for preventing tumor progression and metastasis. Written for cancer physicians and biologists as well as drug discovery and development teams in both industry and academia, this is the first book of its kind which explores novel approaches to inhibit MET and RON kinases other than traditional small molecule kinase inhibitors. These new strategies target key tumorigenic processes on the outside of the cell, such as growth factor activation by proteases. These unique strategies have promising potential as an improved alternative to kinase inhibitors, chemotherapy, or radiation treatment.
The book provides an comprehensive overview on biology, genetics and cellular functions of serpins (serine protease inhibitors) in health and disease. With over 1000 members serpins are the most diverse family of protease inhibitors. Latest groundbreaking research findings are presented and broaden the understanding on inhibitory and non-inhibitory serpins, not only in mammalian organisms but also in insects, worms, plants and viruses.​
Proteases are everywhere from prokaryotes to eukaryotes, from virus to bacteria and in all human tissues, playing a role in many biological functions. Among these functions, the inflammatory reaction is of particular interest. In inflamed tissues, proteases can have a microbial and/or host origin and are involved not only in tissue remodeling, but also in specific signaling to resident or inflammatory cells, thereby contributing to the innate immune response. This volume presents all advances in our knowledge of the role proteases and their inhibitors play in various diseases associated with inflammatory response. Mechanisms involved in protease signaling to cells are presented, and the different types of proteases that are present at inflammatory sites and their effects on the course of inflammation are discussed. Finally, the evidence for considering proteases and their receptors as potential molecular targets for therapeutic interventions in the treatment of inflammatory diseases is discussed in the context of specific organ inflammatory pathologies (the lung, gastrointestinal tract, skin, joints, etc.).
Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The acronym serpin was originally coined because many serpins inhibit chymotrypsin-like serine proteases. This volume of Methods in Ezymology is split into 2 parts and comprehensively covers the subject.
Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. This volume in the Methods in Enzymology series comprehensively covers this topic. With an international board of authors, this volume covers subjects such as Crystallography of serpins and serpin complexes, Serpins as hormone transporters, and Production of serpins using cell free systems. This volume in the Methods in Enzymology series comprehensively covers the topic of serpins With an international board of authors, this volume covers subjects such as Crystallography of serpins and serpin complexes, Serpins as hormone transporters, and Production of serpins using cell free systems
This volume explores the latest methods used to study and define serpin molecular structure, basic protease inhibition, serpin targets, and the roles of serpin in biology and disease using animal models. The chapters in this book cover topics such as crystallography and phage display, peptide design, phospholipid binding, and thrombus formation to microbiome analysis and development. Written in the highly successful Methods in Molecular Biology series format, chapters include 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. Cutting edge and authoritative, Serpins: Methods and Protocols is a valuable resource for researchers and scientists interested in learning more about this evolving field.
This new book with 35 chapters is a comprehensive account of the important features of the pulmonary circulation which will appeal to (1) clinical and non-clinical students who want a broad-based introduction to the subject, (2) postgraduates involved in or contemplating research on the pulmonary circulation, (3) specialists in chest medicine, cardiology and intensive and critical care whose clinical work concerns diseases affecting the pulmonary blood vessels.Pulmonary circulation is well illustrated with 132 figures, 43 tables and learning points highlighted at the end of each chapter. There are two main sections: “Basic Mechanisms” and “Clinical Practice”. All the important features of the pulmonary circulation are reviewed — genetics, cell biology, vascular remodelling, anatomy, physiology, pharmacology, pulmonary hypertension, pulmonary oedema, etc.