Description
This book provides an up to date overview of the multiple roles of NADPH oxidases (Noxes) in human health and disease. Building on the earlier volume NADPH Oxidases Revisited: From Function to Structure, it shifts the focus toward the involvement of Nox enzymes in pathogenic mechanisms and their emerging relevance for therapeutic strategies.
The book highlights the biochemistry, structure, and function of Noxes, with emphasis on structural similarities, regulation of Nox expression, the molecular basis of conversion from resting to activated state, de novo cytochrome design, and their relation to voltage gated proton channels. The book contains a detailed description of Nox products serving as effectors of the microbicidal action of phagocytes (superoxide, peroxynitrite, heme peroxidases) and of the role of NADPH oxidases in inducing ferroptosis. It also places emphasis on the role of Nox-derived reactive oxygen species (ROS), in signaling pathways, with hydrogen peroxide acting as a second messenger. Facing the Nox-derived cytotoxic effectors, the book offers several chapters focused on molecules responsible for antioxidative defense, namely, superoxide dismutases, thioredoxin reductases, and peroxiredoxins. The whole cell aspects of Nox action are addressed in chapters focused on the phagosome and on extracellular traps. A major part of the book deals, as expected from its title, with the contribution of Nox enzymes to the pathogenesis of a broad range of diseases, comprising Nox-related immunodeficiencies, liver fibrosis and cancer, pulmonary fibrosis, inflammatory bowel disease, neurodegenerative diseases, epilepsy, cardiovascular disease, and infertility and discusses the therapeutic potential of targeting Nox mediated pathogenic pathways.
Two essays, a recollection by and a homage to scientists who were active from the infancy of Nox research, serve as an introduction to the book, providing historical context and personal perspectives on the development of Nox research.
Advances in NADPH Oxidases Research: From Molecules to Diseases brings together cellular, molecular, structural, and translational insights, offering a concise yet comprehensive resource for researchers and clinicians interested in the biology and medical relevance of NADPH oxidases.
Part I. Recollections and Homages.- Chapter 1. Falling in Love with Nox2 My Journey to Ithaka (A Scientific Autobiography).- Chapter 2. On Seymour Klebanoff.- Part II. Effector, Signaling, and Protective Molecules.- Chapter 3. The Superoxide Radical: Chemical and Biological Activities.- Chapter 4. Peroxynitrite as a Key Effector in NADPH Oxidase-Related Pathways.- Chapter 5. Mammalian Heme Peroxidases.- Chapter 6. Superoxide Dismutases as Redox Regulators and Therapeutic Targets in Vascular and Neurodegenerative Disease.- Chapter 7. Mammalian Thioredoxin Reductases - Opposing or Facilitating Cellular NADPH Oxidase Activities?.- Chapter 8. NADPH Oxidase and Peroxiredoxins in Cellular Redox Regulation.- Chapter 9. Ferroptosis and NADPH Oxidases.- Chapter 10. Reactive Oxygen Species and Cell Signaling Pathways.- Part III. Biochemistry and Structure.- Chapter 11. EROS, a Crucial Regulator of NOX2: Past, Present, and Future.- Chapter 12. De Novo Cytochrome Design: Bioinspired Proteins as Tools for Interrogating and Manipulating Biological Electron Transfer.- Chapter 13. A Practical Guide to Voltage Gated Proton Channels with Special Focus on their Role in the Phagocyte Respiratory Burst.- Chapter 14. Cryo-EM Structures Illuminate the Activation Mechanism of NOX.- Chapter 15. Structural and Biochemical Investigation of a Bacterial NOX from Streptococcus pneumonia.- Par IV. Cell Biology.- Chapter 16. Death in the Phagosome.- Chapter 17. NOX2 and Neutrophil Extracellular Traps.- Chapter 18. Oxidative Stress and Male Infertility: a Biochemical Odyssey.- Part V. Pathology.- Chapter 19. Advances in Gene Therapy for Chronic Granulomatous Disease.- Chapter 20. RAC2-Related Immunodeficiency.- Chapter 21. The TGF- /NADPH Oxidases Axis in the Regulation of Liver Fibrosis and Cancer.- Chapter 22. NADPH Oxidases and Pulmonary Fibrosis.- Chapter 23. Contribution of NADPH Oxidases to Intestinal Homeostasis and Inflammatory Bowel Disease Pathophysiology.- Chapter 24. NADPH Oxidase in the Mechanism of Neurodegeneration of Parkinson s Disease.- Chapter 25. Pathogenic Mechanisms in Amyotrophic Lateral Sclerosis.- Chapter 26. The Nature of Brain Degenerative Diseases as Reflected by the Genome Instability Disease Ataxia-Telangiectasia.- Chapter 27. NADPH Oxidases and Epilepsy: Pathophysiological Insights and Therapeutic Implications.- Chapter 28. NADPH Oxidases in the Pathology of the Elastic Component of Connective Tissue: Cardiovascular Implications in Marfan and Williams-Beuren Syndromes.
Edgar Pick is Professor Emeritus of Immunology at the Gray Faculty of Medical and Health Sciences, Tel Aviv University. He joined Tel Aviv University after postdoctoral studies at the Scripps Research Foundation, La Jolla, and the University of London and his initial interest was in soluble mediators of cell-mediated immunity (cytokines). Intrigued by the proposal that cytokines promote the bactericidal action of phagocytes by augmenting their production of ROS in response to phagocytosis of microorganisms, he engaged in an in-depth study of the enzyme responsible for the generation of the primordial ROS, the superoxide anion (the NADPH oxidase of phagocytes or Nox2). In the course of a period of four decades, he made fundamental discoveries in this area that comprised: the design of the cell-free system of activating the resting Nox2 in vitro, leading to the discovery that the activation of the membrane-localized enzyme depends on the participation of cytosolic components; the identification of the small GTPase Rac1 as essential for the activation of Nox2; providing proof for the presence of all catalytic redox centers in Nox2; elucidation of the mechanism of dissociation of the Rac1-Rho GDP Dissociation Inhibitor (RhoGDI) complex; the design of a trimeric fusion protein consisting of functionally significant domains in the 3 cytosolic regulators, and the identification of a key domain in Nox2 involved in interaction with the activating regulatory protein p67phox. Edgar Pick was an Editor of the book Biology of the Lymphokines (Academic Press, 1979), coedited with Stanley Cohen (1st coeditor) and Joost J. Oppenheim (3rd coeditor). He also acted as the Editor of the books series Lymphokines , volumes 1-15 (Academic Press, 1980-1988), with Maurice Landy as Advisory Editor. He, recently, edited the book NADPH Oxidases Revisited: From Function to Structure (Springer, Cham, 2023).
