Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Volume 3 - Role in Specific Diseases

1st Edition - December 26, 2013

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  • Editor: M. Hayat
  • Hardcover ISBN: 9780124055292
  • eBook ISBN: 9780124055346

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Description

Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and up-to-date, this book offers a valuable guide to these cellular processes whilst encouraging researchers to explore their potentially important connections. Volume 3 explores the role of autophagy in specific diseases and developments, including: Crohn’s Disease, Gaucher Disease, Huntington’s Disease, HCV infection, osteoarthritis, and liver injury. A full section is devoted to in-depth exploration of autophagy in tumor development and cancer. Finally, the work explores the relationship between autophagy and apoptosis, with attention to the ways in which autophagy regulates apoptosis, and the ways in which autophagy has been explored in Lepidoptera, elucidating the use of larval midgut as a model for such exploration.  From these well-developed foundations, researchers, translational scientists, and practitioners may work to better implement more effective therapies against some of the most devastating human diseases.   Volumes in the Series Volume 1: Molecular Mechanisms. Elucidates autophagy’s association with numerous biological processes, including cellular development and differentiation, cancer, immunity, infectious diseases, inflammation, maintenance of homeostasis, response to cellular stress, and degenerative diseases such as Alzheimer’s, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and prion diseases. Volume 2: Role in General Diseases. Describes the various aspects of the complex process of autophagy in a myriad of devastating human diseases, expanding from a discussion of essential autophagic functions into the role of autophagy in proteins, pathogens, immunity, and general diseases.  Volume 3: Role in Specific Diseases. Explores the role of autophagy in specific diseases and developments, including: Crohn’s Disease, Gaucher Disease, Huntington’s Disease, HCV infection, osteoarthritis, and liver injury, with a full section devoted to in-depth exploration of autophagy in tumor development and cancer, as well as the relationship between autophagy and apoptosis.Volume 4: Mitophagy. Presents detailed information on the role of mitophagy, the selective autophagy of mitochondria, in health and disease, by delivering an in-depth treatment of the molecular mechanisms involved in mitophagy initiation and execution, as well as the role of mitophagy in Parkinson Disease, cardiac aging, and skeletal muscle atrophy. Volume 5: Role in Human Diseases. Comprehensively describes the role of autophagy in human diseases, delivering coverage of the antitumor and protumor roles of autophagy; the therapeutic inhibition of autophagy in cancer; and the duality of autophagy’s effects in various cardiovascular, metabolic, and neurodegenerative disorders.Volume 6: Regulation of Autophagy and Selective Autophagy. Provides coverage of the mechanisms of regulation of autophagy; intracellular pathogen use of the autophagy mechanism; the role of autophagy in host immunity; and selective autophagy. Volume 7: Role of Autophagy in Therapeutic Applications. Provides coverage of the latest developments in autophagosome biogenesis and regulation; the role of autophagy in protein quality control; the role of autophagy in apoptosis; autophagy in the cardiovascular system; and the relationships between autophagy and lifestyle.  Volume 8: Autophagy and Human Diseases. Reviews recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, and introduces new, more effective therapeutic strategies, in the development of targeted drugs and programmed cell death, providing information that will aid on preventing detrimental inflammation.Volume 9: Necrosis and Inflammation in Human Diseases. Emphasizes the role of Autophagy in necrosis and inflammation, explaining in detail the molecular mechanism(s) underlying the formation of autophagosomes, including the progression of Omegasomes to autophagosomes.

Key Features

  • Brings together oncologists, neurosurgeons, physicians, research scientists, and pathologists in the field of autophagy to discuss cutting-edge developments in this rapidly-advancing field
  • Builds upon recent advances in genome-scale approaches and computational tools to discuss the advances in regulation of autophagy at the systems level
  • Organized for readers into easy-to-access sections: molecular mechanisms; role of autophagy in disease; role of autophagy in cancer; and autophagy and apoptosis
  • Explores exciting new developments, including the measurement of autophagic flux; the molecular role of the Atg12-Atg5-Atg16 complex; and the molecular bases of autophagosome formation in yeast

Table of Contents

  • Dedication

    Preface

    Contributors

    Abbreviations and Glossary

    Autophagy: Volume 1–Contributions

    Autophagy: Volume 2–Contributions

    List of Contributions Projected in Volume 4

    Chapter 1. Introduction to Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection and Aging, Volumes 1–4

    Introduction

    Specific Functions of Autophagy (A Summary)

    Autophagy in Normal Mammalian Cells

    Major Types of Autophagies

    Selective Autophagies

    Autophagosome Formation

    Autophagic Lysosome Reformation

    Autophagic Proteins

    Monitoring Autophagy

    Reactive Oxygen Species (ROS)

    Mammalian Target of Rapamycin

    Role of Autophagy in Tumorigenesis and Cancer

    Role of Autophagy in Immunity

    Role of Autophagy in Viral Defense and Replication

    Role of Autophagy in Intracellular Bacterial Infection

    Role of Autophagy in Heart Disease

    Role of Autophagy in Neurodegenerative Diseases

    Cross-Talk between Autophagy and Apoptosis

    Autophagy and Ubiquitination

    Autophagy and Necroptosis

    Pexophagy

    Mitophagy

    Mitochondrial Fusion and Fission

    References

    Part I: Molecular Mechanisms

    Chapter 2. Autophagic Flux, Fusion Dynamics, and Cell Death

    Introduction

    The Current Conception of Autophagic Flux and its Measurement

    Putting a Number to Autophagic Flux

    What is not Autophagic Flux: Pitfalls and Cautions

    Flux, Fusion, and Trafficking Determine Autophagic Function

    Fusion Affects Autophagic Flux

    Trafficking Affects Autophagic Flux

    Physics Modeling of Autophagy

    Tuning Autophagic Flux: Driving Cellular Fate

    Future Outlook

    Acknowledgments

    References

    Chapter 3. Architecture of the Atg12–Atg5–Atg16 Complex and its Molecular Role in Autophagy

    Introduction

    Structure of Atg5

    Structure of Atg16

    Atg5–Atg16 Interaction and its Significance in Autophagy

    Structure of the Atg12–Atg5 Conjugate and its Interaction with Atg3

    Molecular Role of the Atg12–Atg5–Atg16 Complex in Autophagy

    Conclusion

    Acknowledgments

    References

    Chapter 4. The Molecular Mechanisms Underlying Autophagosome Formation in Yeast

    Introduction

    Hierarchical Assembly of Atg Proteins

    Atg1 Kinase and its Regulators

    Atg9 Exists on Unique Vesicles Essential for Autophagy

    The Atg14-Containing PI3K Complex is Involved in Autophagosome Formation

    The Atg2–Atg18 Complex

    Two Ubiquitin-Like Conjugation Systems

    Fine Mapping of the Atg Proteins on the Isolation Membrane

    Concluding Remarks

    References

    Part II: Role of Autophagy in Disease

    Chapter 5. Role of Autophagy in Cell Survival in Liver Injury

    Introduction

    Clearance of Intracellular Protein Aggregates

    Lipid Metabolism

    Viral Infection

    Liver Tumorigenesis

    Drug-Induced Liver Injury

    Conclusion and Closing Remarks

    References

    Chapter 6. Polymorphisms in Autophagy-Related Genes in Crohn’s Disease: Impact on Intracellular Bacteria Persistence and Inflammatory Response

    Introduction

    Host Genetic Susceptibility to IBD

    Microbial Trigger in CD Etiology

    CD-Associated Risk Polymorphisms in Autophagy-Related Genes

    Handling of CD-Associated Bacteria by Autophagy

    Deregulation of IRGM-Dependent Xenophagy in CD

    CD-Associated Mutation Thr300Ala in ATG16L1 Impairs Xenophagy and Antimicrobial Response

    Impaired Autophagy Activation in Cells Expressing CD-Associated NOD2 L1007fsinsC Mutation

    IRGM-, ATG16L1-, and NOD2-Associated Defective Autophagy Leads to Dysregulated Inflammatory Response

    Conclusion

    References

    Chapter 7. Functional Relevance of Autophagins in Life and Disease

    Introduction

    The Atg8 Conjugation System: Role of the Cysteine Proteinase ATG4

    Autophagins: The Mammalian Orthologues of Atg4

    Autophagins in Life and Disease

    Conclusions and Perspectives

    Acknowledgments

    References

    Chapter 8. Strategies to Block Autophagy in Tumor Cells

    Introduction

    Strategies to Block Autophagy

    Conclusions and Future Perspectives

    Acknowledgments

    References

    Chapter 9. Autophagic Dysfunction in Gaucher Disease and its Rescue by Cathepsin B and D Proteases

    Introduction

    Saposin C Deficiency: A Lysosomal Storage Disorder

    Autophagic Dysfunction in Saposin C-Deficient Fibroblasts

    Discussion

    References

    Chapter 10. Cargo Recognition Failure Underlies Macroautophagy Defects in Huntington’s Disease

    Introduction

    Protein Degradation in Huntington’s Disease

    Inefficient Autophagic Elimination of Cytosolic Components Associated with HD

    Therapeutic Strategies for HD Targeting Autophagy

    References

    Chapter 11. Hepatitis C Virus Infection, Autophagy, and Innate Immune Response

    Introduction

    Autophagy in HCV Infection

    Innate Immune Response in HCV Infection

    Pathogen Recognition Receptor Mediated-Signaling in HCV Infection

    HCV-Induced Autophagy and Innate Immunity

    Conclusion

    Acknowledgments

    References

    Chapter 12. Geranylgeranoic Acid Induces Incomplete Autophagy but Leads to the Accumulation of Autophagosomes in Human Hepatoma Cells

    Introduction

    Induction of Autophagy By GGA

    Impairment of Autolysosome Formation

    Discussion

    Acknowledgments

    References

    Chapter 13. Defense Against Proteotoxic Stress in the Heart: Role of p62, Autophagy, and Ubiquitin–Proteasome System

    Introduction into Protein Quality Control

    PQC Insufficiency: A Common Feature of Cardiac Disorders

    Insufficient UPS Function Contributes to Cardiac Disorders

    Autophagy Protects the Heart Against Proteotoxic Stress

    The Role of P62 in Cardiac PQC

    Coordination of the UPS and Autophagy

    Concluding Remarks and Future Directions

    Acknowledgments

    References

    Chapter 14. Elimination of Intracellular Bacteria by Autophagy

    Introduction

    Ubiquitin-Dependent Induction

    Bacterial Sensor-Dependent Induction

    Damaged Vacuole Sensing-Dependent Induction

    Escape from Autophagy

    Concluding Remarks and Perspective

    References

    Chapter 15. Protein Phosphatase 2A Has Positive and Negative Roles in Autophagy

    Introduction

    Protein Phosphatase 2A (PP2A)

    PP2A: A Multifaceted Player in Autophagy

    PP2A, Autophagy, and Disease

    Discussion

    Acknowledgments

    References

    Part III: Role of Autophagy in Cancer

    Chapter 16. Erufosine Induces Autophagy and Apoptosis in Oral Squamous Cell Carcinoma: Role of the Akt–mTOR Signaling Pathway

    Introduction

    Oral Cancer

    Akt–mTOR Signaling Pathway

    Alkylphosphocholines

    Discussion

    References

    Chapter 17. Emerging Role of Hypoxia-Induced Autophagy in Cancer Immunotherapy

    Introduction

    Role of Hypoxia in Tumor Response to Immune Cells

    Autophagy Modulates the Antitumor Immune Response Under Hypoxia

    Perspectives for Improving the Antitumor Immune Response

    Conclusion

    Acknowledgments

    References

    Chapter 18. Involvement of Autophagy and Apoptosis in Studies of Anticancer Drugs

    Introduction

    Autophagy and Cancer

    Apoptosis and Cancer

    Autophagic and Apoptotic Drugs in Breast Cancer

    Autophagic and Apoptotic Drugs in Lung Cancer

    Autophagic and Apoptotic Drugs in Gastric Cancer

    Autophagic and Apoptotic Drugs in Hepatocellular Carcinoma

    Autophagic and Apoptotic Drugs in Colorectal Cancer

    Autophagic and Apoptotic Drugs in Cervical Cancer

    Autophagic and Apoptotic Drugs in Esophagus Cancer

    Autophagic and Apoptotic Drugs in other Cancers

    Conclusion

    Acknowledgments

    References

    Chapter 19. Autophagy-Based Protein Biomarkers for In Vivo Detection of Cardiotoxicity in the Context of Cancer Therapy

    Introduction

    Cancer Chemotherapeutic Agents and Cardiotoxicity

    Autophagy-Based Biomarkers to Detect Cardiotoxicity

    Autophagy-Based Therapeutic Approach for Cancer Treatment and Cardioprotection

    Current Gaps in Knowledge and Opportunities for Future Studies

    Disclosures

    References

    Chapter 20. Inhibition of mTOR Pathway and Induction of Autophagy Block Lymphoma Cell Growth: Role of AMPK Activation

    Introduction

    Adenosine Monophosphate-Activated Protein Kinase (AMPK)

    AMPK: A Therapeutic Target of Lymphoma

    Acknowledgments

    References

    Part IV: Autophagy and Apoptosis

    Chapter 21. Autophagy Regulates Osteoarthritis-Like Gene Expression Changes: Role of Apoptosis and Reactive Oxygen Species

    Introduction

    Autophagy in Human Articular Cartilage Tissues and Human Chondrocytes

    The State of Autophagy in Normal Chondrocytes Under Catabolic Stresses

    The Roles of Autophagy in the Il-1β-Induced Gene Expression Changes

    The Roles of Autophagy in Apoptosis of Human Chondrocytes

    Reactive Oxygen Species

    Reactive Oxygen Species and Osteoarthritis

    The Effect of Rapamycin on the Intracellular ROS Level in Human Chondrocytes

    The Roles of Autophagy in an Experimental OA Model

    Discussion

    References

    Chapter 22. The Key Role of Autophagy and its Relationship with Apoptosis in Lepidopteran Larval Midgut Remodeling

    Introduction

    Autophagy and Apoptosis in Lepidoptera

    The Midgut of Lepidoptera

    Conclusions and Future Perspectives

    Acknowledgments

    References

    Chapter 23. Interferon Regulatory Factor 1 Regulates both Autophagy and Apoptosis in Splenocytes during Sepsis

    Introduction

    Interferon Regulatory Factor-1 (IRF-1)

    Immune Cell Apoptosis in Sepsis

    Immune Cell Autophagy in Sepsis

    Conclusion

    References

    Chapter 24. The Interplay between Autophagy and Apoptosis

    Introduction

    Dual-Function Proteins Regulate Autophagy and Apoptosis

    Cleavage of Atg Proteins by Caspases and Calpains

    Degradation of Apoptosis-Related Proteins by Autophagy

    Discussion

    Acknowledgments

    References

    Index

Product details

  • No. of pages: 432
  • Language: English
  • Copyright: © Academic Press 2014
  • Published: December 26, 2013
  • Imprint: Academic Press
  • Hardcover ISBN: 9780124055292
  • eBook ISBN: 9780124055346

About the Editor

M. Hayat

M. Hayat
Dr. Hayat has published extensively in the fields of microscopy, cytology, immunohistochemistry, immunocytochemistry, and antigen retrieval methods. He is Distinguished Professor, Department of Biological Sciences, Kean University, Union, New Jersey, USA.

Affiliations and Expertise

Distinguished Professor, Department of Biological Sciences, Kean University, Union, NJ, USA

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