Format:
Online-Ressource (VIII, 320 p. 89 illus., 62 illus. in color, digital)
ISBN:
9781461441182
Series Statement:
Advances in Experimental Medicine and Biology 734
Content:
This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.
Note:
Description based upon print version of record
,
Complement Therapeutics; Preface; Contents; Chapter 1: Progress and Trends in Complement Therapeutics; 1.1 Of Dogmas, Challenges, and Opportunities: The Changing Field of Complement Research; 1.2 Finding the Achilles' Heel of Complement, One Disease at a Time; 1.2.1 A Broad Range of Diseases Warrant a Broad Range of Strategies; 1.2.2 Is There an Optimal Point of Intervention?; 1.2.3 Safe Ride or Tightrope Walk? A (Cautious) Risk Assessment; 1.3 A Handyman's Toolbox of Complement Inhibition; 1.3.1 Towards More Selective Protease Inhibitors
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1.3.2 Block It: Protein Interaction Inhibitors from Big to Small1.3.3 Build Your Own Regulator; 1.3.4 A Friendly Reception: Prevention of In fl ammatory Signaling; 1.3.5 Back to the Roots: Exploiting Natural Concepts; 1.4 Aim Before You Shoot: Targeting of Complement Drugs; 1.5 Alternative Concepts; 1.6 Pinpointing Activation Sources: Diagnostic Strategies; 1.7 Conclusions and Outlook; References; Chapter 2: Inhibition of the Serine Proteases of the Complement System; 2.1 The Key Role of Serine Proteases in Cascade Systems; 2.2 Major Types of Protease Inhibitors; 2.3 C1-Inhibitor
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2.4 Small-Molecule Inhibitors2.5 Engineered Protease Inhibitors; 2.6 Conclusions; References; Chapter 3: The Role of MASP-1/3 in Complement Activation; 3.1 Introduction; 3.2 Recognition Molecules Involved in Lectin Pathway Activation; 3.3 Structure and Function of MASPs; 3.4 Character of MASP-1 and MASP-3 (M1/3) Knockout Mouse; 3.4.1 Generation of MASP1/3 Knockout Mouse (M1/3KO); 3.4.2 Lectin Pathway Activation in M1/3 KO Mice; 3.4.3 M1/3KO Mice Lack Activation of the Alternative Complement Pathway; 3.4.4 Proenzyme of Df in M1/3KO Mice; 3.5 Novel Functions of MASP-1 and MASP-3
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3.5.1 Recombinant MASP-1 Cleaves and Activates Pro-Df3.5.2 Characteristics of rMASP-3 and Its Activation; 3.5.3 MASP-3 Activates the Alternative Pathway; 3.6 Concluding Remark; References; Chapter 4: Membrane-Bound Complement Regulatory Proteins as Biomarkers and Potential Therapeutic Targets for SLE; 4.1 Membrane-Bound Complement Regulatory Proteins; 4.1.1 Decay-Accelerating Factor (DAF); 4.1.1.1 History; 4.1.1.2 Distribution; 4.1.1.3 Structure and Molecular Biology of DAF; 4.1.1.4 DAF as Receptor for Pathogens; 4.1.1.5 Functions of DAF; Complement Regulatory Role of DAF
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DAF as a Ligand for Lymphocyte Antigen CD97DAF as a Signal Transducer; DAF in T Cell Immunity; 4.1.2 Membrane Cofactor Protein (MCP, CD46); 4.1.2.1 History; 4.1.2.2 Distribution; 4.1.2.3 Structure and Molecular Biology of MCP; 4.1.2.4 MCP as Receptor for Pathogens; 4.1.2.5 Function of MCP; Complement Regulatory Role of MCP; MCP in Signal Transduction; MCP in Human T Cell Immunity; MCP in Human B Cell Immunity; MCP and In fl ammation; 4.1.3 Complement Receptor 1 (CR1); 4.1.3.1 History; 4.1.3.2 Structure and Molecular Biology of CR1; 4.1.3.3 Functions of CR1; Regulation of Complement Cascade
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Immune Complex Clearance
Additional Edition:
ISBN 9781461441175
Additional Edition:
Buchausg. u.d.T. ISBN 978-1-461-44117-5
Language:
English
Subjects:
Biology
,
Medicine
DOI:
10.1007/978-1-4614-4118-2
URL:
Volltext
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