Fly Models of Human Diseases

Chapter One: Fly Models of Human Diseases: Drosophila as a Model for Understanding Human Mitochondrial Mutations and Disease

• Abstract
• 1 Mitochondria Play Diverse Roles
• 2 Mitochondrial Diseases—Causes and Effects
• 3 How Can Studying Drosophila Contribute to Our Understanding of Human Mitochondrial Diseases?
• 4 Mitochondrial Diseases Caused by mtDNA Mutations
• 5 Disease-Causing Point Mutations Are Most Prevalent in mt:tRNAs—Conservation Between Human and Drosophila
• 6 Drosophila Models of mtDNA-Induced Disease: Untapped Future Potential
• 7 Mitochondrial Inheritance and Quality Control Checkpoints
• 8 Concluding Remarks: Loss of Mitochondrial Function Broadly Impacts Human Disease
• Acknowledgments

Chapter Two: Drosophila as a Model for Human Diseases—Focus on Innate Immunity in Barrier Epithelia

• Abstract
• 1 Introduction
• 2 Evolutionary Conservation of Innate Immunity
• 3 Innate Immunity in Barrier Epithelia
• 4 Epithelial Immunity in the Gastrointestinal Tract of Humans and Drosophila
• 5 Drosophila as a Model for Human Respiratory Organ Diseases Linked to Infection and Inflammation
• 6 Drosophila as a Model of Human Skin Infections and Wound Healing
• 7 Concluding Remarks
• Acknowledgments

Chapter Three: Drosophila melanogaster as a Model of Muscle Degeneration Disorders

• Abstract
• 1 Introduction
• 2 Drosophila Models for Muscular Dystrophies
• 3 Muscle Disease Models Related to Motor Neuron Disorders
• 4 Drosophila Models of Cachexia-Like Wasting
• 5 Therapeutic Potential of Identified in Drosophila Screens Factors
• 6 Conclusions

Chapter Four: Amyotrophic Lateral Sclerosis Pathogenesis Converges on Defects in Protein Homeostasis Associated with TDP-43 Mislocalization and Proteasome-Mediated Degradation Overload

• Abstract
• 1 Introduction
• 2 Current Challenges in ALS Research
• 3 RNA Processing, Splicing, RNA Foci, and Protein Aggregation
• 4 Proteostasis Deficiency in ALS
• 5 SOD-1 and Proteinopathy in ALS
• 6 Prion-Like Protein Toxicity and ALS
• 7 Conclusion and Future Perspective
• Acknowledgments

Chapter Five: Mechanisms of Parkinson's Disease: Lessons from Drosophila

• Abstract
• 1 Introduction
• 2 Drosophila as a Model System for PD
• 3 Dominant Traits
• 4 Recessive Traits
• 5 Functions of the PINK1/Parkin Pathway
• 6 Convergent Therapeutic Approaches
• 7 Concluding Remarks
• Acknowledgments

Chapter Six: Neurotoxicity Pathways in Drosophila Models of the Polyglutamine Disorders

• Abstract
• 1 Introduction
• 2 Transcriptional and Nuclear Dysfunction
• 3 Genetic and Pharmacological Screens for Suppressors of PolyQ Pathology
• 4 Mitochondrial Dysfunction
• 5 Autophagy Defects
• 6 Conclusion

Chapter Seven: AxGxE: Using Flies to Interrogate the Complex Etiology of Neurodegenerative Disease

• Abstract
• 1 Age, Environmental Insult and Genetic Risk in Human Neurodegenerative Disease
• 2 Challenges in Interrogating Contributions from Aging, Genetic Risk Factors and Environmental Insult to Human Neurodegeneration
• 3 Drosophila as a Versatile Model for Investigating Aging, Genetics and Environmental Factors Involved in Neurodegeneration
• 4 The Relevance of Drosophila in a Drug Discovery Pipeline

Chapter Eight: Unraveling the Neurobiology of Sleep and Sleep Disorders Using Drosophila

• Abstract
• 1 What is Sleep, and What Controls Sleep?
• 2 Modeling Sleep in Health and Disease Using Drosophila
• 3 Conclusions
• Acknowledgments

Chapter Nine: Modeling Human Cancers in Drosophila

• Abstract
• 1 Introduction
• 2 Fly Cancer Models
• 3 Drug Discovery
• 4 Conclusion
• Acknowledgments

Chapter Ten: Stem-Cell-Based Tumorigenesis in Adult Drosophila

• Abstract
• 1 Cancer Stem Cells
• 2 Stem-Cell-Based Tumorigenesis in the Adult Drosophila Midgut
• 3 Tumorigenesis Through Stem-Cell Competition in Testis
• 4 Differences Between Normal and CSCs
• 5 Potential Biology Behind the Therapy Resistance of CSCs
• 6 Summary and Perspectives

Chapter Eleven: The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies

• Abstract
• 1 Introduction
• 2 The Prostate
• 3 The Drosophila Accessory Gland—A Key Gland in the Male Reproductive System
• 4 Molecular and Functional Parallels Between Seminal Fluid Proteins in Flies and Humans
• 5 Development and Cellular Organization of the Accessory Gland
• 6 Functions of the Adult Secondary Cell
• 7 Modeling Prostate Cancer Biology in Secondary Cells
• Acknowledgments

Chapter Twelve: Drosophila melanogaster Models of Galactosemia

• Abstract
• 1 Galactose Metabolism via the Leloir Pathway
• 2 A D. melanogaster Model of Classic Galactosemia
• 3 A D. melanogaster Model of Epimerase Deficiency Galactosemia
• 4 A D. melanogaster Model of Kinase Deficiency Galactosemia
• 5 Conclusions
• Acknowledgments

Chapter Thirteen: Drosophila as a Model for Diabetes and Diseases of Insulin Resistance

• Abstract
• 1 Introduction
• 2 Sugar Metabolism in Drosophila and Humans
• 3 Drosophila Models of Type 1 Diabetes
• 4 Modeling Insulin-Dependent Sugar Uptake and Insulin Release in Drosophila
• 5 Drosophila as a Model for Insulin Resistance and Type 2 Diabetes
• 6 Are Glucose and Trehalose Metabolism Regulated Independently in Drosophila?
• 7 Drosophila as a Model for Obesity-Related Heart Disease
• 8 Drosophila as a Model for Metabolic Syndrome
• 9 From Correlation to Causation: Drosophila as a Model to Study Gene Function in Metabolism
• 10 Concluding Remarks
• Acknowledgments