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Informationen zum Autor Frederick R. Maxfield, PhD , is Professor and Chair of the Department of Biochemistry at Weill Cornell Medical College. He has used digital imaging microscopy to characterize pH changes in endocytic organelles, to measure the kinetics of transport of molecules among organelles, and to identify new endocytic organelles such as the endocytic recycling compartment. Dr. Maxfield has published extensively on trafficking of lipids and cholesterol. James M. Willard, PhD , has been a member of the Phospholipidosis Working Group at the Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration since 2005 and Co-Chair of the group since 2011. Shuyan Lu, MSc , has been an Investigative Toxicologist of Drug Research and Development at Pfizer for over 10 years. She studies the role of lysosomal pathways and physical chemical properties of compounds in drug-induced toxicity. Klappentext Discussing recent findings, up-to-date research, and novel strategies, the book integrates perspectives from pharmacology, toxicology, and biochemistry to illustrate the potential of lysosomes in drug discovery and development.* Explores basic principles and properties of lysosomes that allow them to act as regulators of cell metabolism, therapeutic targets, and sites for activation of drug conjugates* Discusses the role of lysosomes in metabolism, drug targeting, apoptosis, cancer, aging, inflammation, autophagy, metabolism, toxicity, and membrane repair* Introduces new pathways in therapeutic development and new mechanisms in drug development Zusammenfassung This book comprehensively reviews lysosomes principles, properties, and role in disease and therapeutics and features perspectives from cell biology, pharmacology, toxicology, and biochemistry to illustrate their drug discovery and development potential. Inhaltsverzeichnis PREFACE xiii LIST OF CONTRIBUTORS xvii 1 Lysosomes: An Introduction 1 Frederick R. Maxfield 1.1 Historical Background, 2 References, 4 2 Lysosome Biogenesis and Autophagy 7 Fulvio Reggiori and Judith Klumperman 2.1 Introduction, 7 2.2 Pathways to the Lysosomes, 10 2.2.1 Biosynthetic Transport Routes to the Lysosome, 10 2.2.2 Endocytic Pathways to the Lysosome, 10 2.2.3 Autophagy Pathways to the Lysosome, 12 2.2.4 The ATG Proteins: The Key Regulators of Autophagy, 14 2.3 Fusion and Fission between the Endolysosomal and Autophagy Pathways, 16 2.3.1 Recycling Endosomes and Autophagosome Biogenesis, 16 2.3.2 Autophagosome Fusion with Late Endosomes and Lysosomes, 17 2.3.3 Autophagic Lysosomal Reformation, 18 2.4 Diseases, 19 2.4.1 Lysosome-Related Disorders (LSDs), 19 2.4.2 Lysosomes in Neurodegeneration and Its Links to Autophagy, 20 2.4.3 Autophagy-Related Diseases, 20 2.5 Concluding Remarks, 22 Acknowledgments, 23 References, 23 3 Multivesicular Bodies: Roles in Intracellular and Intercellular Signaling 33 Emily R. Eden, Thomas Burgoyne, and Clare E. Futter 3.1 Introduction, 33 3.2 Downregulation of Signaling by Sorting onto ILVs, 35 3.3 Upregulation of Signaling by Sorting onto ILVs, 38 3.4 Intercellular Signaling Dependent on Sorting onto ILVs, 39 3.5 Conclusion, 44 References, 45 4 Lysosomes and Mitophagy 51 Dominik Haddad and Patrik Verstreken 4.1 Summary, 51 4.2 Mitochondrial Significance, 51 4.3 History of Mitophagy, 52 4.4 Mechanisms of Mitophagy, 53 4.4.1 Mitophagy in Yeast, 54 4.4.2 Mitophagy in Mammals, 55 4.5 Conclusion, 57 Acknowledgments, 57 References, 58 5 Lysosome Exocytosis and Membrane Repair 63 Rajesh K. Singh and Abiga...
