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Drosophila gives an overview of the ways in which Drosophila is currently being used as a model organism to further our understanding of a spectrum of human neurological diseases. Each chapter is written by respected researchers and gives an excellent account of the subject that is suitable for postgraduate and postdoctoral researchers.
This book is aimed at generating an updated reservoir of scientific endeavors undertaken to unravel the complicated yet intriguing topic of neurodegeneration. Scientists from Europe, USA and India who are experts in the field of neurodegenerative diseases have contributed to this book. This book will help readers gain insight into the recent knowledge obtained from Drosophila model, in understanding the molecular mechanisms underlying neurodegenerative disorders and also unravel novel scopes for therapeutic interventions. Different methodologies available to create humanized fly models that faithfully reflects the pathogenicities associated with particular disorders have been described here. It also includes information on the exciting area of neural stem cells. A brief discussion on neurofibrillary tangles, precedes the elaborate description of lessons learnt from Drosophila about Alzheimer's, Parkinson’s, Spinomuscular Atrophy, Huntington’s diseases, RNA expansion disorders and Hereditary Spastic Paraplegia. We have concluded the book with the use of Drosophila for identifying pharmacological therapies for neurodegenerative disorders. The wide range of topics covered here will not only be relevant for beginners who are new to the concept of the extensive utility of Drosophila as a model to study human disorders; but will also be an important contribution to the scientific community, with an insight into the paradigm shift in our understanding of neurodegenerative disorders. Completed with informative tables and communicative illustrations this book will keep the readers glued and intrigued. We have comprehensively anthologized the lessons learnt on neurodegeneration from Drosophila and have thus provided an insight into the multidimensional aspects of pathogenicities of majority of the neurodegenerative disorders.
The term neurodegeneration refers to the progressive loss of neurons leading to the onset of irreversible neurodegenerative disorders like the Alzheimer's disease (AD). We have harnessed the genetics of the Drosophila melanogaster a.k.a fruit fly to elucidate the complex network of genetic and molecular mechanisms underlying neurodegeneration. We exploited the vast plethora of sophisticated genetic tools available at our disposal to mimic the neurodegenerative disease in the fly eye. Alzheimer's disease is a common form of dementia with no cure to date. One of the hallmarks of this disease is the accumulation of Amyloid plaques that triggers neuronal death. The Amyloid Precursor Protein (APP) is a trans-membrane protein which when properly cleaved forms a 40 amino acid long polypeptide but when improperly cleaved forms a 42 amino acid long polypeptide (Aß42) which is hydrophobic in nature. We believe that once these Aß42 plaques are formed they emanate certain signals that cause the healthy neurons to die. Thus it is important to identify these signals in order to delay the onset of the Aß42 mediated neurodegeneration. In order to ascertain the molecular and genetic mechanisms underlying the Aß42 mediated neurodegeneration in Alzheimer's disease several animal models have been developed. We have utilized the Drosophila eye model to understand the etiology of the disease by identifying genetic and chemical modifiers that could ameliorate the Aß42 mediated neurodegenerative phenotype. Here we discuss about one such modifier Wingless (Wg) which when downregulated or blocked rescues the Aß42 mediated neurodegeneration. A complete understanding of a disease-associated brain requires the analysis of the individual neurons. Studies till now have focused on understanding the onset of Alzheimer's disease by misexpressing the Alzheimer associated proteins in a certain group of cells with the help of the yeast derived GAL4-UAS system. In order to understand how the Aß42 plaques produced in a small group of neurons slowly spreads across the entire brain, we must understand the crosstalk between the plaque forming neurons and the surrounding healthy neurons. We thus have generated a two-clone system in order to study the fate of the surrounding wild type neurons and have seen that the Aß42 misexpressed neurons grow at the expense of the adjacent wild type neurons.
Most biological pathways, physical and neurological properties are highly conserved between humans and Drosophila and nearly 75% of human disease-causing genes have a functional homologue in Drosophila. This volume provides recent advances in Drosophila models for various human diseases, with each chapter providing a review of studies involving Drosophila models, as well as detailed protocols commonly used in laboratories. Starting with a review of Drosophila’s value as a highly tractable model organism for studying human diseases, subsequent chapters present Drosophila models for specific human diseases. The book provides a useful resource for all scientists who are starting to use the Drosophila model in their studies, and for researchers working in the pharmaceutical industry and using new screening models to develop new medicines for various diseases.
Motor neuron diseases are the most catastrophic of neurodegenerative disorders. The cognitive function is spared, but the motor neuron degeneration translates into progressive muscle weakness and paralysis that propel the afflicted patient to eventual death. Neurodegenerative disorders constitute one of the major challenges of modern medicine in view of the current lack of effective therapies. The fruit fly, Drosophila melanogaster, has a distinguished history as an important model organism capable of shaping our fundamental understanding of life. Remarkably, the vast majority of all known human disease genes have a similar fly counterpart and at the molecular and physiological level, the basic principles of neuromuscular function are amazingly conserved between humans and Drosophila. Combine this with the presence of numerous genetic tools developed over the last century allowing genes and the proteins they encode to be manipulated swiftly to decipher their in vivo function and you have a superb genetic animal model organism of disease.This publication singles out the past and recent accomplishments of Drosophila in modelling motor neuron disease including amyotrophic lateral sclerosis (Lou Gehrigs disease), hereditary spastic paraplegias, Charcot-Marie-Tooth disease, spinal and bulbar muscular atrophy (Kennedys disease) and spinal muscular atrophy. The emphasis is on recent developments including the emerging molecular pathways underpinning these disorders. Genetic screens aimed at identifying novel genes that cause motor neuron degeneration or finding modifiers of the phenotype resulting from the disruption of disease-causative genes are also tackled. Importantly, this collection provides an inspiring look at the indispensability of the fruit fly, and of model organisms in general, to neuroscience research.
In recent years, medical developments have resulted in an increase in human life expectancy. The editors have extensive knowledge and experience in this field and the book is aimed at undergraduates, postgraduates, and academics. The chapters cover Alzheimer's disease, Parkinson's disease, Huntington's, and other neurodegenerative disorders.
This book contains 12 chapters divided into two sections. Section 1 is "Drosophila - Model for Genetics." It covers introduction, chromosomal polymorphism, polytene chromosomes, chromosomal inversion, chromosomal evolution, cell cycle regulators in meiosis and nongenetic transgenerational inheritance in Drosophila. It also includes ecological genetics, wild-type strains, morphometric analysis, cytostatics, frequencies of early and late embryonic lethals (EEL and LEL) and mosaic imaginal discs of Drosophila for genetic analysis in biomedical research. Section 2 is "Drosophila - Model for Therapeutics." It explains Drosophila as model for human diseases, neurodegeneration, heart-kidney metabolic disorders, cancer, pathophysiology of Parkinson's disease, dopamine, neuroprotective therapeutics, mitochondrial dysfunction and translational research. It also covers Drosophila role in ubiquitin-carboxyl-terminal hydrolase-L1 (UCH-L1) protein, eye development, anti-dUCH antibody, neuropathy target esterase (NTE), organophosphorous compound-induced delayed neuropathy (OPIDN) and hereditary spastic paraplegia (HSP). It also includes substrate specificities, kinetic parameters of recombinant glutathione S-transferases E6 and E7 (DmGSTE6 and DmGSTE7), detoxification and insecticidal resistance and antiviral immunity in Drosophila.