Matrix Proteases in Health and Disease
(Sprache: Englisch)
Presenting a comprehensive overview of the multifaceted field of extracellular matrix degradation by extracellular proteases, this reference focuses on the recently elucidated functions of proteolytic systems, such as plasminogen activators, ADAMS and other...
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Presenting a comprehensive overview of the multifaceted field of extracellular matrix degradation by extracellular proteases, this reference focuses on the recently elucidated functions of proteolytic systems, such as plasminogen activators, ADAMS and other matrix proteases in physiological and pathological tissue remodeling. It specifically addresses the role of extracellular proteases in cancer cell invasion, stroke and Alzheimer's disease, describing the basic biochemistry behind these disease states, as well as therapeutic strategies based on protease inhibition.
With its trans-disciplinary scope, this reference bridges the gap between fundamental research and biomedical and pharmaceutical application, making this required reading for basic and applied scientists in the molecular life sciences.
With its trans-disciplinary scope, this reference bridges the gap between fundamental research and biomedical and pharmaceutical application, making this required reading for basic and applied scientists in the molecular life sciences.
Klappentext zu „Matrix Proteases in Health and Disease “
Presenting a comprehensive overview of the multifaceted field of proteases in the extracellular matrix environment, this reference focuses on the recently elucidated functions of complex proteolytic systems in physiological and pathological tissue remodeling. The proteases treated include both serine proteases such as plasminogen activators and TTSPs, metalloproteases such as MMPs and ADAMS and cysteine protease cathepsins. The text specifically addresses the role of extracellular proteases in cancer cell invasion, stroke and infectious diseases, describing the basic biochemistry behind these disease states, as well as therapeutic strategies based on protease inhibition. With its trans-disciplinary scope, this reference bridges the gap between fundamental research and biomedical and pharmaceutical application, making this required reading for basic and applied scientists in the molecular life sciences.
Presenting a comprehensive overview of the multifaceted field of proteases in the extracellular matrix environment, this reference focuses on the recently elucidated functions of complex proteolytic systems in physiological and pathological tissue remodeling. The proteases treated include both serine proteases such as plasminogen activators and TTSPs, metalloproteases such as MMPs and ADAMS and cysteine protease cathepsins. The text specifically addresses the role of extracellular proteases in cancer cell invasion, stroke and infectious diseases, describing the basic biochemistry behind these disease states, as well as therapeutic strategies based on protease inhibition.
With its trans-disciplinary scope, this reference bridges the gap between fundamental research and biomedical and pharmaceutical application, making this required reading for basic and applied scientists in the molecular life sciences.
With its trans-disciplinary scope, this reference bridges the gap between fundamental research and biomedical and pharmaceutical application, making this required reading for basic and applied scientists in the molecular life sciences.
Inhaltsverzeichnis zu „Matrix Proteases in Health and Disease “
PrefaceIntroduction MATRIX PROTEASES AND THE DEGRADOME Introduction Bioinformatic Tools for the Analysis of Complex Degradomes Evolution of Mammalian Degradomes Human Diseases of Proteolysis Matrix Proteases and Their Inhibitors THE PLASMINOGEN ACTIVATION SYSTEM IN NORMAL TISSUE REMODELING Introduction Biochemical and Enzymological Fundamentals Biological Roles of the Plasminogen Activation System Tissue Remodeling Processes Conclusions PHYSIOLOGICAL FUNCTIONS OF MEMBRANE-TYPE METALLOPROTEASES Introduction Historical Perspective Activation of the Activator Potential Roles of MT-MMPs and Discovery of a Human MMP Mutation MT-MMP Function? Physiological Roles of MT1-MMP in the Mouse MT1-MMP Function in Lung Development MT1-MMP Is Required for Root Formation and Molar Eruption Identification of Cooperative Pathways for Collagen Metabolism MT-MMP Activity in the Hematopoietic Environment Physiological Role of MT2-MMP MT-Type MMPs Work in Concert to Execute Matrix Remodeling 67MT4-MMP - an MT-MMP with Elusive Function MT5-MMP Modulates Neuronal Growth and Nociception Summary and Concluding Remarks BONE REMODELING: CATHEPSIN K IN COLLAGEN TURNOVER IntroductionProteolytic Machinery of Bone Resorption and Cathepsin K Specificity and Mechanism of Collagenase Activity of Cathepsin K Role of Glycosaminoglycans in Bone Diseases Development of Specific Cathepsin K Inhibitors and Clinical Trials Off-Target and Off-Site Inhibition Conclusion TYPE-II TRANSMEMBRANE SERINE PROTEASES: PHYSIOLOGICAL FUNCTIONS AND PATHOLOGICAL ASPECTS Introduction Functional/Structural Properties of TTSPs Physiology and Pathobiology PLASMINOGEN ACTIVATORS IN ISCHEMIC STROKE Introduction Rationale for Thrombolysis after Stroke Preclinical Studies The Association of Endogenous tPA with Excitotoxic and Ischemic Brain Injury Mechanistic Studies of tPA in Excitotoxic and Ischemic Brain Injury tPA and the Blood-Brain Barrier-PDGF-CC Summary BACTERIAL ABUSE OF MAMMALIAN EXTRACELLULAR PROTEASES DURING TISSUE
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INVASION AND INFECTION Introduction Tissue and Cell Surface Remodeling Proteases Proteases of the Blood Coagulation and the Fibrinolytic System Contact System Conclusion and Future Prospectives EXPERIMENTAL APPROACHES FOR UNDERSTANDING THE ROLE OF MATRIX METALLOPROTEINASES IN CANCER INVASION Introduction: Functional Roles of MMPs in Physiological Processes Involving the Induction and Sustaining of Cancer Invasion EMT: a Prerequisite of MMP-Mediated Cancer Invasion or a Coordinated Response to Growth-Factor-Induced MMPs? Escape from the Primary Tumor: MMP-Mediated Invasion of Basement Membranes Invasive Front Formation: Evidence for MMP Involvement In Vivo Invasion at the Leading Edge: MMP-Mediated Proteolysis of Collagenous Stroma Tumor Angiogenesis and Cancer Invasion: MMP-Mediated Interrelationships Cancer Cell Intravasation: MMP-Dependent Vascular Invasion Cancer Cell Extravasation: MMP-Dependent Invasion of the Endothelial Barrier and Subendothelial Stroma Metastatic Site: Involvement of MMPs in the Preparation, Colonization, and Invasion of Distal Organ Stroma Perspectives: MMPs in the Early Metastatic Dissemination and Awakening of Dormant Metastases PLASMINOGEN ACTIVATORS AND THEIR INHIBITORS IN CANCER Introduction The Plasminogen Activator System PROTEASE NEXIN-1 - A SERPIN WITH A POSSIBLE PROINVASIVE ROLE IN CANCER Introduction - Serpins and Cancer History of PN-1 General Biochemistry of PN-1 Inhibitory Properties of PN-1 Binding of PN-1 and PN-1-Protease Complexes to Endocytosis Receptors of the Low-Density Lipoprotein Receptor Family Pericellular Functions of PN-1 in Cell Cultures PN-1 Expression Patterns Functions of PN-1 in Normal Physiology Functions of PN-1 in Cancer Conclusions SECRETED CYSTEINE CATHEPSINS - VERSATILE PLAYERS IN EXTRACELLULAR PROTEOLYSIS Introduction Structure and Function of Cysteine Cathepsins Synthesis, Processing, and Sorting of Cysteine Cathepsins Extracellular Enzymatic Activity of Lysosomal Cathepsins Endogenous Cathepsin Inhibitors as Regulators of Extracellular Cathepsins Extracellular Substrates of Cysteine Cathepsins Cysteine Cathepsins in Cancer: Clinical Associations Cysteine Cathepsins in Cancer: Evidence from Animal Models Molecular Dysregulation of Cathepsins in Cancer Progression Extracellular Cathepsins in Cancer Conclusions and Further Directions ADAMS IN CANCER ADAMs-Multifunctional Proteins ADAMs in Tumors and Cancer Progression ADAMs in Cancer - Key Questions Yet to Be Answered The Clinical Potential of ADAMs Concluding Remarks UROKINASE-TYPE PLASMINOGEN ACTIVATOR, ITS RECEPTOR AND INHIBITOR AS BIOMARKERS IN CANCER Introduction Breast Cancer Colorectal Cancer Lung Cancer Gynecological Cancers Prostate Cancer Conclusion and Perspectives CLINICAL RELEVANCE OF MMP AND TIMP MEASUREMENTS IN CANCER TISSUE Introduction MMP Structure MMP Biology and Pathology Natural Inhibitors of MMPs Regulation of MMP Function Cancer Stromal Cell Production of MMPs Anticancer Effects of MMPs Tissue Levels of MMPs and TIMPs in Cancer Patients Conclusions NEW PROSPECTS FOR MATRIX METALLOPROTEINASE TARGETING IN CANCER THERAPY Introduction Lessons Learned from Preclinical and Clinical Studies of MMPIs in Cancer and Possible Alternatives Novel Generation of MMPIs Exploit MMP Function to Improve Drug Bioavailability Conclusion
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Autoren-Porträt
Niels Behrendt is a research group leader at the Finsen Laboratory at the Rigshospitalet (Copenhagen University Hospital), Denmark. He obtained his Ph.D. in 1989 and his D.Sc. degree from Copenhagen University in 2004. The main focus of his work is in protease-dependent tissue remodeling, the interplay of these processes with other cellular functions and their role in cancer invasion.
Bibliographische Angaben
- 2012, XXII, 394 Seiten, 3 farbige Abbildungen, 13 Schwarz-Weiß-Abbildungen, Maße: 17,9 x 24,7 cm, Gebunden, Englisch
- Herausgegeben: Niels Behrendt
- Verlag: Wiley-VCH
- ISBN-10: 3527329919
- ISBN-13: 9783527329915
- Erscheinungsdatum: 14.06.2012
Sprache:
Englisch
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