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This Methods in Molecular Biology book offers methods for studying inflammasome function, including generation of inflammasome stimuli, monitoring of caspase-1 activity and processing, activation of IL-1β cytokines, plus lab protocols, material lists and tips.
The inflammasome was first described in 2002 as a molecular complex activating proinflammatory caspases and therefore regulating the maturation and biological activities of cytokines such as IL-1 and IL-18. This finding was substantiated by the identification of several mutations in the cias1 gene, encoding the human NLRP3 protein, responsible for several autoinflammatory disorders such as the Muckle Wells syndrome. Since, the interest for this complex has constantly increased and several inflammasome complexes with different specificities have been described. These inflammasomes sense a wide variety of pathogens and danger signals and are key players in the inflammatory response. With the contributions of leading international experts in the field, this book provides an extensive overview of the current knowledge of inflammasome biology and their role in health and disease.
DNA Sensors and Inflammasomes, Volume 625, the latest release in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. New sections in this release include Phosphorylation and dimerization of STING and IRF3, cGAS enzymology, Synthesis and identification of immuno-stimulatory CDNs, Tracking cGAS activity/ cGAMP formation using SPR/NMR, Using an enzyme coupled assay to track cGAS activity under steady states, Tracking the polymerization of DNA sensors, inflammasome receptors, and downstream signaling partners using FRET, NLRC4 structure, Tracking TREX1 activity, DNA association and dissociation kinetics of PARP1, and more.
The inflammasome is a protein complex composed of an intracellular sensor—typically a Nod-like receptor (NLR), the precursor procaspase-1, and the adaptor ASC. Inflammasome activation leads to the maturation of caspase-1 and the processing of its substrates, IL-1β and IL-18. The inflammasome has been implicated numerous diseases, and blockade of inflammasome-derived IL-1β has beneficial effects on several of these diseases. Different books have been edited about the biology of inflammasomes and about methods to study, however, the implication of this complex in the different diseases and pathological conditions show the need of a book about the clinical implications and therapeutic options. This project will show the context where inflammasomes are being studied and the molecular implications in the medical and clinical contexts. Other important topic of the inflammasomes will be the development of pharmacological inhibitors in order to improve new clinical applications. In this sense, we can find new drugs with inhibitory effects or old drugs with an inhibitory potential effect. There is a need for re-establishing the real benefits of the inflammasome inhibitions in pathological situations and the management of the differents diseases where inflammasomes are implicated.
Inflammasome Biology: Fundamentals, Role in Disease States, and Therapeutic Opportunities is a complete reference on the role of inflammasomes in health and disease. Sections cover the different types of inflammasomes, including cellular signaling, structural and evolutive aspects, overview the role of inflammasomes in key diseases, microbial infections and human body systems conditions, cover the interplay between Inflammasomes and cell death processes, and discuss current therapeutic opportunities driven by inflammasome research, including targeting, blocking and inhibiting the development of inflammasomes through both synthetic and natural compounds. This book is the perfect reference for cell biologists, immunologists and research clinicians to understand the foundations of inflammasomes and explore the therapeutic opportunities they present. Pharma researchers may also find this reference invaluable in devising new approaches to developing anti-inflammatory drugs. - Provides comprehensive coverage of the subject of inflammasome biology - Authored by leading experts worldwide - Provides biological insights that have both health implications and therapeutic potential
Inflammation triggers specific metabolic pathways and if not resolved, translates into several painful diseases such as rheumatoid arthritis, lupus, Alzheimer's disease, cardiovascular disorders and psoriasis. Various processes have been explored to understand the factors behind inflammation and consequently, many mechanisms have been examined to suppress it. The nucleotide-binding domain like receptor 3 (NLRP3) inflammasome is an example of such factors which is responsible for triggering sterile and microbe induced inflammation. Studies of genetic variants of the related gene have revealed insights into the mRNA expression pathways that may help researchers to identify crucial disease mechanisms. This book is a review of the scientific findings of distinguished scholars who have studied NLRP3 inflammasome activation and its contribution in worsening the outcomes of inflammatory disorders. This collection of chapters covers many aspects of the multifaceted role of NLRP3 inflammasome. Beginning with airway inflammation and fibrosis, it progresses to explore its involvement in pulmonary hypertension, heart diseases, tuberculosis, cardiovascular complications, and childhood asthma. Additionally, it examines the inflammasome's impact on protozoan parasitic infections and neuropathic pain. The chapters not only elucidate the intricate mechanisms of NLRP3 activation but also discuss potential inhibitors and therapeutic targets. Readers will gain a comprehensive understanding of the NLRP3 inflammasome's diverse implications across different physiological contexts. The book includes references making this book a valuable treatise of insights for researchers, clinicians, and healthcare professionals.
The structure, functions, and interactions of myeloid cells have long been the focus of research and therapeutics development. Yet, much more remains to be discovered about the complex web of relationships that makes up the immune systems of animals. Scientists today are applying genome-wide analyses, single-cell methods, gene editing, and modern imaging techniques to reveal new subclasses of differentiated myeloid cells, new receptors and cytokines, and important interactions among immune cells. In Myeloid Cells in Health and Disease: A Synthesis, Editor Siamon Gordon has assembled an international team of esteemed scientists to provide their perspectives of myeloid cells during innate and adaptive immunity. The book begins by presenting the foundational research of Paul Ehrlich, Elie Metchnikoff, and Donald Metcalf. The following chapters discuss evolution and the life cycles of myeloid cells; specific types of differentiated myeloid cells, including macrophage differentiation; and antigen processing and presentation. The rest of the book is organized by broad topics in immunology, including the recruitment of myeloid and other immune cells following microbial infection the role of myeloid cells in the inflammation process and the repair of damaged tissue the vast arsenal of myeloid cell secretory molecules, including metalloproteinases, tumor necrosis factor, histamine, and perforin receptors and downstream signaling pathways that are activated following ligand-receptor binding roles of myeloid cells during microbial and parasite infections contributions of myeloid cells in atherosclerosis myeloid-derived suppressor cells in tumor development and cancer Myeloid Cells in Health and Disease: A Synthesis will benefit graduate students and researchers in immunology, hematology, microbial pathogenesis, infectious disease, pathology, and pharmacology. Established scientists and physicians in these and related fields will enjoy the book's rich history of myeloid cell research and suggestions for future research directions and potential therapies.
Lipid Signaling and Metabolism provides foundational knowledge and methods to examine lipid metabolism and bioactive lipid signaling mediators that regulate a broad spectrum of biological processes and disease states. Here, world-renowned investigators offer a basic examination of general lipid, metabolism, intracellular lipid storage and utilization that is followed by an in-depth discussion of lipid signaling and metabolism across disease areas, including obesity, diabetes, fatty liver disease, inflammation, cancer, cardiovascular disease and mood-related disorders. Throughout, authors demonstrate how expanding our understanding of lipid mediators in metabolism and signaling enables opportunities for novel therapeutics. Emphasis is placed on bioactive lipid metabolism and research that has been impacted by new technologies and their new potential to transform precision medicine. - Provides a clear, up-to-date understanding of lipid signaling and metabolism and the impact of recent technologies critical to advancing new studies - Empowers researchers to examine bioactive lipid signaling and metabolism, supporting translation to clinical care and precision medicine - Discusses the role of lipid signaling and metabolism in obesity, diabetes, fatty liver disease, inflammation, cancer, cardiovascular disease and mood-related disorders, among others
This book, the first complete textbook on this novel field in Medicine, comprehensively covers the clinical presentation, pathogenesis, genetics, and latest management strategies for autoinflammatory disorders as well as the basic science of autoinflammation. Relevant concepts such as how translational science of genetics and immunology relates to the innate immune system and autoinflammation are covered. Descriptions of the monogenic and polygenic/complex diseases that fall under the umbrella of autoinflammatory diseases are provided. Further topics covered include the latest clinical and genetic diagnostic approaches, concepts on the relationship between autoinflammation and autoimmunity/immunodeficiency, the role of autoinflammation in cancer, treatments and management strategies for these diseases, and potential areas of future development. The Textbook of Autoinflammation systematically describes and reviews diagnostic and treatment options for autoinflammatory disorders as well as all aspects of the concept of autoinflammation, and represents a valuable resource for professionals in a variety of disciplines who encounter these patients or who study autoinflammation.
This volume details our current understanding of the architecture and signaling capabilities of known canonical and non-canonical inflammasome complexes and highlights their action, in particular in response to infection with important bacterial model organisms and the corresponding disease pathologies. The first chapters review new insights into the assembly and structures of inflammasome components and emphasize general strategies of up- and downstream signaling events. In addition, the authors specifically discuss the composition and activity of inflammasomes during infection with various gut pathogens (Salmonella, Shigella, Yersinia, Listeria and Helicobacter), respiratory pathogens (Mycobacterium, Legionella, Burkholderia and Streptococcus) as well as skin and soft tissue pathogens (Francisella and Staphylococcus). The discoveries presented provide a better understanding of the cellular and molecular biology of inflammasomes, which will pinpoint important new therapeutic targets for the treatment and prevention of multiple infectious diseases in the future. It is a valuable resource for students, scientists and clinicians, providing up-to-date information on this emerging research topic.