Lysosomes. Biology, Diseases, And Therapeutics

140,26 € 134,87 €
Disponible
ISBN
9781118645154
Edición
Autores
Frederick R. Maxfield, James M. Willard, Shuyan Lu
Editorial
Wiley
Fecha Publicacion
30 ago. 2016
Características
N/D
Contents List of Contributors Preface/Foreword (Will come) Chapter 1: Lysosomes an Introduction Frederick R. Maxfield 1.1. Historical Background References Chapter 2: Lysosome biogenesis and autophagy Fulvio Reggiori, Judith Klumperman 2.1. Introduction 2.2. Pathways to the lysosomes 2.3. Fusion and fission between the endo-lysosomal and autophagy pathways 2.4. Diseases 2.5. Concluding remarks Acknowledgements References Chapter 3: Multivesicular bodies: roles in intracellular and intercellular signaling Emily R. Eden, Thomas Burgoyne, Clare E. Futter 3.1. Introduction 3.2. Down regulation of signaling by sorting onto ILVs - 3.3. Up regulation of signaling by sorting onto ILVs 3.4. Intercellular signaling dependent on sorting onto ILVs 3.5. Conclusions References Chapter 4: Lysosomes and mitophagy Dominik Haddad, Patrik Verstreken 4.1. Summary 4.2. Mitochondrial significance 4.3. History of mitophagy 4.4. Mechanisms of mitophagy 4.5. Conclusion Acknowledgments References Chapter 5: Lysosome Exocytosis and Membrane Repair Rajesh K. Singh, Abigail S. Haka 5.1. Introduction 5.2. Functions of Lysosome Exocytosis 5.2.1. Specialized Lysosome Related Organelles 5.2.2. Lysosome Exocytosis for Membrane Repair 5.2.3. Lysosome Exocytosis as a Source of Membrane 5.2.4. Lysosome Exocytosis for Extracellular Degradation 5.2.5. Lysosome Exocytosis and Delivery of Proteins to the Cell Surface 5.3. Mechanisms of Lysosome Exocytosis 5.3.1. Maturation of Lysosomes and Lysosome Related Organelles 5.3.2. Transport of Lysosomes to the Plasma Membrane 5.3.3. Tethering of Lysosomes to the Plasma Membrane 5.3.4. Lysosome Fusion with the Plasma Membrane 5.4. Conclusions Acknowledgements References Chapter 6: Role of lysosomes in lipid metabolism Frederick R. Maxfield 6.1. Introduction 6.2. Endocytic uptake of lipoproteins 6.3. Lipid metabolism in late endosomes and lysosomes 6.4. Autophagy and lysosomal lipid turnover 6.5. Lysosomal lipid hydrolysis and metabolic regulation 6.6. Summary References Chapter 7: TFEB, master regulator of cellular clearance Graciana Diez-Roux and Andrea Ballabio 7.1. The lysosome 7.2. The transcriptional regulation of lysosomal function 7.3. TFEB subcellular regulation is regulated by its phosphorylation 7.4. A lysosome-to-nucleus signaling mechanism 7.5. TFEB and cellular clearance in human disease References Chapter 8: Lysosomal membrane permeabilization in cell death Urška Repnik, Boris Turk 8.1. Introduction 8.2. Cell death modalities 8.3. Lysosomal membrane permeabilization (LMP) and cell death 8.4. Conclusions Acknowledgements References Chapter 9: The Lysosome in Aging-Related Neurodegenerative Diseases Ralph A. Nixon 9.1. Introduction 9.2. Lysosome function in aging organisms 9.3. Lysosomes and diseases of late age onset 9.4. Lysosomes in aging-related neurodegenerative diseases 9.5. Conclusions Acknowledgements References Chapter 10: Lysosome and cancer Marja Jäättelä and Tuula Kallunki 10.1. Introduction 10.2. Lysosomal function and its importance for cancer development and progression 10.3. Cancer-induced changes in lysosomal function 10.4. Cancer-induced changes in lysosome composition 10.5. Changes in the lysosomal membrane proteins 10.6. Molecular changes involving lysosomal integrity 10.7. Conclusion  References Chapter 11: The Genetics Of Sphingolipid Hydrolases & Sphingolipid Storage Diseases Edward H. Schuchman and Calogera M. Simonaro 11.1. Introduction & Overview 11.2. Acid Ceramidase Deficiency: Farber Disease 11.3. Acid Sphingomyelinase Deficiency:  Types A and B Niemann-Pick Disease 11.4. Beta-Glucocerebrosidase Deficiency:  Gaucher Disease 11.5. Galactocerebrosidase Deficiency:  Krabbe Disease/Globoid Cell Leukodystrophy 11.6. Arylsulfatase A Deficiency:  Metachromatic Leukodystrophy 11.7. Alpha Galactosidase A Deficiency:  Fabry Disease   11.8. Beta Galactosidase Deficiency:  GM1 Gangliosidosis           11.9. Hexosaminidase A & B Deficiency:  GM2 Gangliosidoses  11.10. Sphingolipid Activator Proteins References Chapter 12: Lysosome-related organelles: modifications of the lysosome paradigm Adriana R. Mantegazza and Michael S. Marks 12.1. Differences between LROs and secretory granules 12.2. Physiological functions of LROs. 12.3. LRO biogenesis 12.4. LRO motility, docking and secretion 12.5. LROs and immunity to pathogens 12.6. Perspectives Acknowledgments References Chapter 13: Autophagy inhibition as a strategy for cancer therapy Xiaohong Ma, Shengfu Piao, Quentin Mcafee, and Ravi K. Amaravadi 13.1. Stages and steps of autophagy 13.2. Induction of autophagy 13.3. Studies in mouse models unravel the dual roles of autophagy in tumor biology 13.4. Clinical Studies on autophagy’s dual role in tumorigenesis 13.5. Mouse models provide the rationale for autophagy modulation in the context of cancer therapy 13.6. Multiple druggable targets in the autophagy pathway 13.7. Overview of preclinical autophagy inhibitors and evidence supporting combination with existing and new anticancer agents 13.8. Proximal autophagy inhibitors 13.9. Quinolines: From antimalarials to  prototypical distal autophagy inhibitors. 13.9.1. Summary for the clinical trials for CQ/HCQ 13.9.2. Developing more potent anticancer autophagy inhibitors 13.10. Summary, Conclusion, and Future Directions References Chapter 14: Autophagy enhancers, are we there yet? Shuyan Lu & Ralph A Nixon 14.1. Introduction 14.2. Autophagy impairment and diseases 14.3. Autophagy enhancer screening 14.4. Concluding Remarks References Chapter 15: Pharmacological Chaperones as Potential Therapeutics for Lysosomal Storage Disorders: Preclinical Research to Clinical Studies Robert E. Boyd, Elfrida R. Benjamin, Su Xu, Richie Khanna, and Kenneth J. Valenzano 15.1. Introduction 15.2. Fabry Disease 15.3. Gaucher Disease 15.4. GM2 Gangliosidoses (Tay-Sachs/Sandhoff Diseases) 15.5. Pompe Disease 15.6. PC-ERT Combination Therapy References Chapter 16: Endosomal Escape Pathways for Delivery of Biologics Philip L. Leopold 16.1. Introduction 16.2. Endosome characteristics 16.3. Delivery of nature’s biologics: lessons on endosomal escape from pathogens 16.4. Endosomal escape using engineered systems 16.5. Conclusion References Chapter 17: Lysosomes and Antibody Drug Conjugates Michelle Mack, Jennifer Kahler, Boris Shor, Michael Ritchie, Maureen Dougher, Matthew Sung, and Puja Sapra 17.1. Introduction 17.2. Receptor Internalization 17.3. Antibody Drug Conjugates 17.4. Mechanisms of Resistance to ADCs 17.5. Summary References Chapter 18: The mechanisms and therapeutic consequences of amine-containing drug sequestration in lysosomes Nadia Hamid and Jeffrey P. Krise 18.1. Introduction 18.2. Lysosomal trapping overview 18.3. Techniques to assess lysosomal trapping 18.4. Influence of lysosomotropism on drug activity 18.5. Influence of lysosomal trapping on pharmacokinetics 18.6. Pharmacokinetic drug-drug interactions involving lysosomes References Chapter 19: Lysosome dysfunction: an emerging mechanism of xenobiotic-induced toxicity Shuyan Lu, Bart Jessen, Yvonne Will & Greg Stevens 19.1. Introduction 19.2. Compounds that impact lysosomal function 19.3. Cellular consequences 19.4. Impairment lysosomal function as a mechanism for organ toxicity 19.5. Concluding Remarks References Chapter 20: Lysosomes and Phospholipidosis in Drug Development and Regulation James M. Willard and Albert De Felice 20.1. Introduction 20.2. FDA involvement 20.3. Autophagy and DIPL 20.4. Early experience with lethal DIPL 20.5. Clinical and non-clinical expressions of DIPL 20.6. Physical Chemistry 20.7. Quantitative Structure-Activity Relationship(QSAR) 20.8. Toxicogenomics 20.9. Fluorescence, dye and immunohistochemical methods for screening 20.10. FDA database and QSAR modelling 20.11. Linking phospholipidosis and overt toxicity 20.12. Phospholipidosis and QT interval prolongation 20.13. DIPL Mechanisms 20.14. Treatment 20.15. Discussion 20.16. Future Directions and Recommendations References Index Author Information 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.
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