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This book presents the reader with an understanding of the role played by matrix metalloproteinases (MMPs) in the normal and diseased central nervous system (CNS). These enzymes may be important to brain development, and may also contribute to tissue destruction, which is observed with inflammatory and degenerative conditions of the brain. The book provides a background on the biology of MMPs, and on the stimuli and conditions that are linked to an increase in their production and activity. It describes the targets of MMPs, which include matrix proteins such as collagen, soluble cytokines and chemokines, and cell surface receptors. Studies implicating MMPs in neuronal process outgrowth and cell migration in CNS development are covered. The book also touches on studies suggesting that, in certain situations, dysregulated MMP activity and/or production may be critical to blood-brain barrier breakdown and neuronal damage./a
In this volume of Methods in Enzymology and its companion Volume 244, the chapters on specific methods, enzymes, and inhibitors are organized within the rational framework of the new systems for classificationand nomenclature. A wide variety of specificities of peptide bond hydrolysis are represented in each set of peptidases, together with an equally wide range of biological functions. Key Features * Aspartic peptidases * Metallopeptidases * New information on classification of proteolytic enzymes * Medical implications of research in this area * Biotechnological uses of these enzymes.
Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.
Multiple sclerosis is a chronic and often disabling disease of the nervous system, affecting about 1 million people worldwide. Even though it has been known for over a hundred years, no cause or cure has yet been discovered-but now there is hope. New therapies have been shown to slow the disease progress in some patients, and the pace of discoveries about the cellular machinery of the brain and spinal cord has accelerated. This book presents a comprehensive overview of multiple sclerosis today, as researchers seek to understand its processes, develop therapies that will slow or halt the disease and perhaps repair damage, offer relief for specific symptoms, and improve the abilities of MS patients to function in their daily lives. The panel reviews existing knowledge and identifies key research questions, focusing on: Research strategies that have the greatest potential to understand the biological mechanisms of recovery and to translate findings into specific strategies for therapy. How people adapt to MS and the research needed to improve the lives of people with MS. Management of disease symptoms (cognitive impairment, depression, spasticity, vision problems, and others). The committee also discusses ways to build and financially support the MS research enterprise, including a look at challenges inherent in designing clinical trials. This book will be important to MS researchers, research funders, health care advocates for MS research and treatment, and interested patients and their families.
Clinical Neurimmunology is the major reference text in the field, providing broad and comprehensive coverage of the interaction between the nervous and immune systems in both normal and diseased states. Understanding this interaction is fundamental to developing therapeutic approaches to disease and injury of the nervous system that are currently only marginally amenable to therapy. Neuroimmunology is a well-recognised and growing specialty world wide, both at the basic science and clinical level. It is a fast moving field and this is the most up to date text available. Chapters are dedicated to the role of the immune system in disorders affecting both the central and peripheral nervous systems, including important neurodegenerative diseases (such as multiple sclerosis and HIV-related neural degeneration) which cause life-long disability. Extensive coverage is given to a whole array of immune-directed therapies. The book has a strong international team of well respected, high profile editors and authors. The first edition published to extensive and positive reviews and has established itself as the principal reference source in the field. This second edition summarizes recent advances in clinical neuroimmunology in a comprehensive and unbiased way.
These volumes teach readers to think beyond apoptosis and describes all of the known processes that cells can undergo which result in cell death This two-volume source on how cells dies is the first, comprehensive collection to cover all of the known processes that cells undergo when they die. It is also the only one of its kind to compare these processes. It seeks to enlighten those in the field about these many processes and to stimulate their thinking at looking at these pathways when their research system does not show signs of activation of the classic apoptotic pathway. In addition, it links activities like the molecular biology of one process (eg. Necrosis) to another process (eg. apoptosis) and contrasts those that are close to each. Volume 1 of Apoptosis and Beyond: The Many Ways Cells Die begins with a general view of the cytoplasmic and nuclear features of apoptosis. It then goes on to offer chapters on targeting the cell death mechanism; microbial programmed cell death; autophagy; cell injury, adaptation, and necrosis; necroptosis; ferroptosis; anoikis; pyronecrosis; and more. Volume 2 covers such subjects as phenoptosis; pyroptosis; hematopoiesis and eryptosis; cyclophilin d-dependent necrosis; and the role of phospholipase in cell death. Covers all known processes that dying cells undergo Provides extensive coverage of a topic not fully covered before Offers chapters written by top researchers in the field Provides activities that link and contrast processes to each other Apoptosis and Beyond: The Many Ways Cells Die will appeal to students and researchers/clinicians in cell biology, molecular biology, oncology, and tumor biology.
Interactions between the immune and nervous systems are involved in many disease processes. Modulation of inflammation can provide an important opportunity to enhance regeneration within the central nervous system. This authoritative book defines the key cellular players in mounting an inflammatory response and highlights critical factors in the target organ that influence the nature of that response and its capacity either to damage or protect the brain. Several key clinical areas are highlighted - particularly autoimmune diseases of the nervous system including multiple sclerosis, as well as microbiological and traumatic challenges; the book therefore provides both a summary of the basic science background as well as practical, clinical-friendly guidelines to management. The book will be of interest to a wide range of physicians, including neurologists, neurosurgeons, neurorehabilitationists, infectious disease physicians, and clinical neuroscientists, as well as neuroscientists and immunologists.
Within the past few years, it has become recognized that the immune system communicates to the brain. Substances released from activated immune cells (cytokines) stimulate peripheral nerves, thereby signaling the brain and spinal cord that infection/inflammation has occurred. Additionally, peripheral infection/inflammation leads to de novo synthesis and release of cytokines within the brain and spinal cord. Thus, cytokines effect neural activation both peripherally and centrally. Through this communication pathway, cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor markedly alter brain function, physiology and behavior. One important but underrecognized aspect of this communication is the dramatic impact that immune activation has on pain modulation. The purpose of this book is to examine, for the first time, immune-to-brain communication from the viewpoint of its effect on pain processing. It is aimed both at the basic scientist and health care providers, in order to clarify the major role that substances released by immune cells play in pain modulation. This book contains chapters contributed by all of the major laboratories focused on understanding how cytokines modulate pain. These chapters provide a unique vantage point from which to examine this question, as the summarized work ranges from evolutionary approaches across diverse species, to the basics of the immune response, to the effect of cytokines on peripheral and central nervous system sites, to therapeutic potential in humans.