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TEXTBOOK : AUTOPHAGY - A DOUBLE-EDGED SWORD - CELL SURVIVAL OR DEATH?

AUTOPHAGY

Edited by Yannick Bailly .

522 pages .
Open Access .


Autophagy has recently benefited from rapid research progress in the field, and this master regulator of cell homeostasis is currently viewed as a valuable biomedical marker for a number of physiological processes and pathological mechanisms underlying major diseases.
Autophagy is known to exert cytoprotection in different cellular contexts, and autophagy induction generally prolongs life. Nevertheless, autophagy is necessary for tissue removal and can trigger cell death in certain situations. These opposed cytoprotective and cell death initiating roles, as well as tissue and time-dependent regulation of autophagy underscore the complexity of the autophagy pathway, and the importance of elucidating the molecular mechanisms controlling autophagy in cell survival and death. Based on the significant effects of autophagy deficiency on the development and pathogenesis of several disorders in animal models, recent research has yielded amazing results with autophagy-targeted pharmacological treatments of diseases. As recently stated by researchers in this field, the reality of autophagy-targeted therapy is now closer than ever expected or predicted.
This book focuses on autophagy relationships with cell death and disease, highlighting the most challenging aspects of current research, and the latest insights into the molecular mechanisms underlying autophagy.
Recent years have seen a growing interest in the different routes to cell death. Although apoptosis and autophagy have been previously considered as two different cell death pathways, one currently envisions a continuum of cell death mechanisms because it is now recognized that autophagy can induce apoptosis. Indeed, when the autolysosomal pathway is deregulated, autophagy can lead to cell death, either as a precursor of apoptosis in apoptosis-sensitive cells, or as a destructive cell digestion process. Whereas autophagy can selectively degrade survival factors and thereby initiate cell death, autophagy can also activate apoptosis by selectively degrading apoptotic inhibitors. This novel idea that autophagy comes into play in the balance between survival and death has major implications in the design of strategies for counteracting the pathophysiological processes. Further understanding of how autophagy is regulated should promote new therapeutic strategies that can ultimately treat a number of diseases, including myopathies, lysosomal storage diseases, cancers, infectious diseases, diabetes, liver diseases, as well as major neurodegenerative diseases which involve impaired autophagic elimination of misfolded proteins ( Alzheimer’s, Parkinson’s, Huntington’s and prion diseases). If autophagy induction is to be considered as a promising therapeutic strategy for neurodegenerative diseases, the dark side of autophagy must be taken into account. For the moment, it remains unclear whether deficits in autophagy provoke neurodegeneration or result from the neurodegenerative status. The data suggest that disrupting autophagy goes hand in hand with neurodegeneration, and a cause and effect relationship may contribute to neuronal damage. Transient, short-termed autophagy is protective, but turns deleterious when autophagy is chronically activated or excessively maintained in neurons. As reviewed in several chapters of the present book, this doubleedged nature of autophagy will ultimately be critical for the development of autophagy-targeted therapeutics, not only for neurodegenerative diseases, but also for infectious diseases and cancer, where pathogens and cancer cells hijack the autophagic machinery for their survival and proliferation.


Yannick Bailly
Neuronal Cytology and Cytopathology,
Institute of Cellular and Integrative Neurosciences,
Department of Neurotransmission & Neuroendocrine Secretion,
University of Strasbourg, France


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CONTENTS  :



Section 1 New Insights into Mechanisms of Autophagy .


 1 Role of Human WIPIs in Macroautophagy 3 Tassula Proikas-Cezanne and Daniela Bakula

2 Atg8 Family Proteins — Autophagy and Beyond 13 Oliver H. Weiergräber, Jeannine Mohrlüder and Dieter Willbold

 3 Rab GTPases in Autophagy 47 Yuko Hirota, Keiko Fujimoto and Yoshitaka Tanaka

 4 Flow Cytometric Measurement of Cell Organelle Autophagy 65 N. Panchal, S. Chikte, B.R. Wilbourn, U.C. Meier and G. Warnes

Section 2 Consequences of Autophagy Deficits .


 5 Autophagy, the “Master” Regulator of Cellular Quality Control: What Happens when Autophagy Fails? 81 A. Raquel Esteves, Catarina R. Oliveira and Sandra Morais Cardoso

6 Altering Autophagy: Mouse Models of Human Disease 121 Amber Hale, Dan Ledbetter, Thomas Gawriluk and Edmund B. Rucker III

Section 3 Autophagy in GNE Myopathy .


 7 Autophagy in GNE Myopathy 141 Anna Cho and Satoru Noguchi

Section 4 Autophagy and the Liver .


 8 Autophagy and the Liver 165 Ricky H. Bhogal and Simon C. Afford

Section 5 Autophagy in Cancer .


 9 Role of Autophagy in Cancer and Tumor Progression 189 Bassam Janji, Elodie Viry, Joanna Baginska, Kris Van Moer and Guy Berchem

10 Role of Autophagy in Cancer 217 Michiko Shintani and Kayo Osawa

11 Regulation of Autophagy by Short Chain Fatty Acids in Colon Cancer Cells 235 Djamilatou Adom and Daotai Nie

 12 Natural Compounds and Their Role in Autophagic Cell Signaling Pathways 249 Azhar Rasul and Tonghui Ma

Section 6 Autophagy in Infectious Diseases .


 13 Infectious Agents and Autophagy: Sometimes You Win, Sometimes You Lose 269 Patricia Silvia Romano

 14 Autophagic Balance Between Mammals and Protozoa: A Molecular, Biochemical and Morphological Review of Apicomplexa and Trypanosomatidae Infections 289 Thabata Lopes Alberto Duque, Xênia Macedo Souto, Valter Viana de Andrade-Neto, Vítor Ennes-Vidal and Rubem Figueiredo Sadok Menna-Barreto

 15 Induction of Autophagy by Anthrax Lethal Toxin 321 Aiguo Wu, Yian Kim Tan and Hao A. Vu

16 Up-Regulation of Autophagy Defense Mechanisms in Mouse Mesenchymal Stromal Cells in Response to Ionizing Irradiation Followed by Bacterial Challenge 331 Nikolai V. Gorbunov, Thomas B. Elliott, Dennis P. McDaniel, K. Lund, Pei-Jyun Liao, Min Zhai and Juliann G. Kiang

Section 7 Autophagy in Neurodegenerative Diseases .


 17 Role of Autophagy in Parkinson’s Disease 353 Grace G.Y. Lim, Chengwu Zhang and Kah-Leong Lim

 18 Neuronal Autophagy and Prion Proteins 377 Audrey Ragagnin, Aurélie Guillemain, Nancy J. Grant and Yannick J. R. Bailly

Section 8 Autophagy and Cell Death .


 19 Role of Autophagy in the Ovary Cell Death in Mammals 423 M.L. Escobar, O.M. Echeverría and G.H. Vázquez-Nin

 20 Autophagy in Development and Remodelling of Mammary Gland 443 Malgorzata Gajewska, Katarzyna Zielniok and Tomasz Motyl

 21 Integrin and Adhesion Regulation of Autophagy and Mitophagy 465 Eric A. Nollet and Cindy K. Miranti

 22 Time Flies: Autophagy During Ageing in Drosophila 487 Sebastian Wolfgang Schultz, Andreas Brech and Ioannis P. Nezis .





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