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Intracellular Traffic And Neurodegenerative Disorders
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Author :Peter H. St.George-Hyslop Publisher :Springer Science & Business Media ISBN 13 :3540879412 Total Pages :188 pages Book Rating :4.5/5 (48 download)
Book Synopsis Intracellular Traffic and Neurodegenerative Disorders by : Peter H. St.George-Hyslop
Download or read book Intracellular Traffic and Neurodegenerative Disorders written by Peter H. St.George-Hyslop and published by Springer Science & Business Media. This book was released on 2009-02-03 with total page 188 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many adult onset neurodegenerative diseases arise from the accumulation of misfolded peptides. This book examines the role sub-cellular trafficking pathways play in the pathological accumulation of these misfolded proteins and in attempts to clear them.
Book Synopsis Trafficking Inside Cells by : Nava Segev
Download or read book Trafficking Inside Cells written by Nava Segev and published by Springer Science & Business Media. This book was released on 2010-05-30 with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.
Book Synopsis The Molecular and Cellular Basis of Neurodegenerative Diseases by : Michael S. Wolfe
Download or read book The Molecular and Cellular Basis of Neurodegenerative Diseases written by Michael S. Wolfe and published by Academic Press. This book was released on 2018-03-29 with total page 561 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer's, Parkinson's, frontotemporal dementia, ALS, Huntington's, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. - Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features - Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration - Details features, advantages and limitations of animal models, as well as prospects for therapeutic development - Authored by internationally recognized leaders in the field - Includes illustrations that help clarify and consolidate complex concepts
Book Synopsis An Investigation of the Intracellular Trafficking of Two Pathological Proteins by : Kathleen FitzGerald
Download or read book An Investigation of the Intracellular Trafficking of Two Pathological Proteins written by Kathleen FitzGerald and published by . This book was released on 2004 with total page 172 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endocytosis is a process whereby cargo is transported to and from the plasma membrane, and between organelles, in membrane-bound vesicles. The HIV encoded Nef protein is immunosuppressive and substantially contributes to the overall state of immune dysfunction associated with acquired immune deficiency syndrome. The pathological Nef protein has been implicated in modifying the receptor-mediated endocytic pathway. The transmissible spongiform encephalopathies caused by the infectious prion protein from a group of fatal neurodegenerative disorders that affect both animals and human. The trafficking of the prion protein is considered to play an essential role in its pathogenic conversion while the route and mechanism of the pathological prion protein remain controversial. The objective of this work was to investigate the intracellular trafficking of these two pathological proteins, Nef and prion, with emphasis on the localization and effects of Nef on proteins associated with the receptor-mediated endocytic pathway and emphasis on the cellular trafficking of the prion protein. Nef localizes primarily to the early sorting endosome and shows dramatic effects on the redistribution of the recycling compartment-associated proteins, Rab 11 and REM-1. Expression of the Nef mutant E160A, which is disrupted in its' ability to recruit the adaptor protein complex AP-3, resulted in a redistribution of the Rab11-positive compartment while having no effect on the localization of the RME-1 positive tubules. In contrast, expression of the Nef mutant LL164/165AA, which is disrupted in its' ability to recruit AP-1 and AP-3, results in a normal recycling compartment phenotype. These results suggest that Nefs' effect on the receptor-mediated endocytic pathway relies on its' ability to interact with adaptor protein complexes. A proportion of the pathological prion protein localized to the Rab4-positive early sorting endosome and recycling compartment. Analysis of the Rab4-positive compartment revealed that the form of the prion protein present was unglycosylated. Subsequently it was shown that trafficking of the prion protein through the caveolar pathway converged with the receptor-mediated endocytic pathway. The cause and significance of two distint pathways converging, with respect to prion protein trafficking, remains to be determined. This work raises the possibility that conversion may take place in the Rab4-positive compartment as it is consistent with previous data stating that conversion from normal to infectious prion protein takes place in an acidic environment similar to that found in endosomes and that conversion of the prion protein favours the unglycosylated form of the protein.
Book Synopsis Modeling the Aggregation of Interacting Neurofilaments in the Axon by : Susan J. Foss
Download or read book Modeling the Aggregation of Interacting Neurofilaments in the Axon written by Susan J. Foss and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: An axon is a long, thin projection away from a neuron. Axonal transport, a crucial process for the survival of a neuron, is the transport of various organelles and proteins along microtubules, which act as an intracellular highway. Disruptions of axonal transport is associated with many neurodegenerative disorders such as motor neuron diseases (including ALS), Alzheimer's disease, and Huntington's disease. In these diseases, we frequently observe local accumulations of cargoes, which resemble highway traffic jams with pileups of cars. It has been hypothesized that these diseases result from "intracellular traffic jams" caused by the interactions of cargoes. In this thesis, we test this hypothesis using a stochastic model that describes cargoes as interacting particles that switch between different moving and pausing states. Specifically, we apply this model to the transport of neurofilaments. Our results suggest that, although the model can generate traffic jams under certain parameter regimes, these jams may be fundamentally different from those observed in diseases. Another conclusion of this model is that low processivity of the molecular motors that transport neurofilaments help avoid intracellular jams. This explains the evolutionary question, "why is the system is designed this way?".
Book Synopsis Dopamine Handbook by : Leslie L. Iversen
Download or read book Dopamine Handbook written by Leslie L. Iversen and published by . This book was released on 2010 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery of dopamine in 1957-1958 was one of the seminal events in the development of modern neuroscience, and has been extremely important for the development of modern therapies of neurological and psychiatric disorders. Dopamine has a fundamental role in almost all aspects of behavior: from motor control to mood regulation, cognition and addiction and reward, and dopamine research has been unique within the neurosciences in the way it has bridged basic science and clinical practice. Over the decades research into the role of dopamine in health and disease has been in the forefront of modern neuroscience. The Dopamine Handbook is the first single-volume publication to capture current progress and excitement in this dynamic research field.
Book Synopsis Axonal Transport of the Parkinson's Disease Protein Alpha-Synuclein by : Eric Anderson
Download or read book Axonal Transport of the Parkinson's Disease Protein Alpha-Synuclein written by Eric Anderson and published by . This book was released on 2017 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt: The intracellular transport of protein complexes, membrane-bound vesicles, organelles, and RNA along microtubule (MT) tracks to the axonal terminal is crucial for neuronal survival and function. In neurodegenerative disorders, such as Parkinson's disease (PD), defects in the axonal transport pathway are suggested to be major contributors to neurodegeneration. a-syn (a-syn) is a small acid protein that is actively transported from the cell body to the axonal terminal and is the main constituent of Lewy bodies (LB), abnormal deposits of protein in the brain in PD. In my dissertation research, I have focused on the mechanism of a-syn transport in axons. The effects of familial PD (fPD) mutations on the transport of a-syn and synaptic proteins were also studied using Drosophila melanogaster (fruit flies) as a model organism. I have found that the aggregate-prone non-amyloidal component (NAC) region in a-syn was required for the dimerization and membrane binding for a-syn during its transport to the axonal terminal. Deletion of a-syn NAC region (delNAC) resulted in an increase in its accumulation within cell bodies located in the brain, decreased its entry into axons, and its transport to the axonal terminal. This decrease in the transport of delNAC to the axonal terminal is due to decreased membrane interaction of a-syn. I have also demonstrated that increased levels of a-syn (3-fold increase mimicking gene triplication in PD or fPD mutation (Alanine53Threoine, A53T)) accumulation in axons disrupt the axonal transport of synaptic proteins, resulting in synaptic morphological defects and locomotion behavior defects. This accumulation of Îł-syn in axons is likely due to dimerization of Îł-syn through the NAC region, possibly on membranes. Therefore, this part of the study revealed an important role for the NAC region in mediating a-syn dimerization on membranes for a-syn transport to the axonal terminal. The second part of the study focused on the effects of a-syn on Rab3 motility. The Rab3 protein, a neuronal guanosine triphosphate (GTP)-binding protein, has been proposed to present together with a-syn on vesicles and has a similar function in regulating synaptic vesicle trafficking. In vivo live image analysis showed disruption of Rab3 motility with excess or fPD mutant a-syn, and mutant Rab3 disrupted the transport of a-syn-containing vesicle to the axonal terminal. Thus, this study highlights, for the first time, a potential interaction between Rab3 and a-syn in the axonal transport pathway. Collectively, these studies provided new insights into our understanding of the a-syn protein in the axonal transport pathway. Alteration in the axonal transport pathway can have important implications in PD, thus, elucidating the mechanism of a-syn protein transport and Îł-syn-mediated disruption of the axonal transport pathway is critical to our overall understanding of the contribution of this pathway to the disease progression.
Book Synopsis Neuroanatomy and Pathology of Sporadic Parkinson's Disease by : Heiko Braak
Download or read book Neuroanatomy and Pathology of Sporadic Parkinson's Disease written by Heiko Braak and published by Springer. This book was released on 2008-12-03 with total page 119 pages. Available in PDF, EPUB and Kindle. Book excerpt: The synucleinopathy sporadic Parkinson’s disease (sPD) is the second most frequent degenerative disorder of the human nervous system after Alzheimer’s disease. The propensity for developing sPD exists in all ethnic groups worldwide, and the prevalence of the disorder increases considerably with age, thereby imposing an enormous social and economic burden on societies with increased life expectancy. The sPD-associated pathological process is progressive, does not go into remission, and can take decades to reach its culmination if it is not be terminated prematurely by death owing to other causes. Against the background of the normal morphology and anatomy, the authors analyze the pathoanatomy of sPD in the nervous system at various neuropathological stages and summarize the potential functional consequences of the lesions.
Book Synopsis Polyglutamine Disorders by : Clévio Nóbrega
Download or read book Polyglutamine Disorders written by Clévio Nóbrega and published by Springer. This book was released on 2018-02-09 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a cutting-edge review of polyglutamine disorders. It primarily focuses on two main aspects: (1) the mechanisms underlying the pathologies’ development and progression, and (2) the therapeutic strategies that are currently being explored to stop or delay disease progression. Polyglutamine (polyQ) disorders are a group of inherited neurodegenerative diseases with a fatal outcome that are caused by an abnormal expansion of a coding trinucleotide repeat (CAG), which is then translated in an abnormal protein with an elongated glutamine tract (Q). To date, nine polyQ disorders have been identified and described: dentatorubral-pallidoluysian atrophy (DRPLA); Huntington’s disease (HD); spinal–bulbar muscular atrophy (SBMA); and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). The genetic basis of polyQ disorders is well established and described, and despite important advances that have opened up the possibility of generating genetic models of the disease, the mechanisms that cause neuronal degeneration are still largely unknown and there is currently no treatment available for these disorders. Further, it is believed that the different polyQ may share some mechanisms and pathways contributing to neurodegeneration and disease progression.
Book Synopsis Disruption of the Intracellular Trafficking of Ganglioside GM1 in a Genetically Accurate Model of the Neurodegenerative Storage Disease Juvenile Neuronal Ceroid-lipofuscinosis by : Aleksandra Somogyi
Download or read book Disruption of the Intracellular Trafficking of Ganglioside GM1 in a Genetically Accurate Model of the Neurodegenerative Storage Disease Juvenile Neuronal Ceroid-lipofuscinosis written by Aleksandra Somogyi and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Magnesium in the Central Nervous System by : Robert Vink
Download or read book Magnesium in the Central Nervous System written by Robert Vink and published by University of Adelaide Press. This book was released on 2011 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.
Book Synopsis Lysosomes by : Frederick R. Maxfield
Download or read book Lysosomes written by Frederick R. Maxfield and published by John Wiley & Sons. This book was released on 2016-06-22 with total page 586 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discussing recent findings, up-to-date research, and novel strategies, the book integrates perspectives from pharmacology, toxicology, and biochemistry to illustrate the potential of lysosomes in drug discovery and development. • Explores basic principles and properties of lysosomes that allow them to act as regulators of cell metabolism, therapeutic targets, and sites for activation of drug conjugates • Discusses the role of lysosomes in metabolism, drug targeting, apoptosis, cancer, aging, inflammation, autophagy, metabolism, toxicity, and membrane repair • Introduces new pathways in therapeutic development and new mechanisms in drug development
Book Synopsis Neurodegenerative Diseases by : Uday Kishore
Download or read book Neurodegenerative Diseases written by Uday Kishore and published by BoD – Books on Demand. This book was released on 2013-05-15 with total page 642 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.
Book Synopsis RNA Metabolism in Neurodegenerative Diseases by : Rita Sattler
Download or read book RNA Metabolism in Neurodegenerative Diseases written by Rita Sattler and published by Springer. This book was released on 2018-06-18 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer’s disease, Huntington’s disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.
Book Synopsis Scanning Electron Microscopy for the Life Sciences by : Heide Schatten
Download or read book Scanning Electron Microscopy for the Life Sciences written by Heide Schatten and published by Cambridge University Press. This book was released on 2013 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: A guide to modern scanning electron microscopy instrumentation, methodology and techniques, highlighting novel applications to cell and molecular biology.
Book Synopsis Quality Control of Cellular Protein in Neurodegenerative Disorders by : Uddin, Md. Sahab
Download or read book Quality Control of Cellular Protein in Neurodegenerative Disorders written by Uddin, Md. Sahab and published by IGI Global. This book was released on 2020-02-14 with total page 515 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein misfolding and aggregation are hallmarks of several neurodegenerative proteinopathies. Though multiple factors like aging, oxidative stress, mitochondrial dysfunction, proteotoxic insults, genetic inconsistency, etc. are responsible for the dysfunction of the neuronal protein quality control system, targeting protein quality control has become an auspicious approach to halt the propagation of neurodegeneration. Quality Control of Cellular Protein in Neurodegenerative Disorders provides diverse aspects exploring the role of the protein quality control in neurodegenerative disorders and potential therapeutic strategies to combat the development and propagation of neurodegeneration. Featuring coverage on a broad range of topics such as molecular chaperones, protein misfolding, and stress signaling, this book is ideally designed for neurobiologists, neuropsychologists, neurophysiologists, medical professionals, neuropathologists, researchers, academicians, students, and practitioners engaged in studies of the protein quality control system in neuronal cells.
Book Synopsis Organelle Contact Sites by : Mitsuo Tagaya
Download or read book Organelle Contact Sites written by Mitsuo Tagaya and published by Springer. This book was released on 2017-08-16 with total page 254 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the first comprehensive coverage of the quickly evolving research field of membrane contact sites (MCS). A total of 16 chapters explain their organization and role and unveil the significance of MCS for various diseases. MCS, the intracellular structures where organellar membranes come in close contact with one another, mediate the exchange of proteins, lipids, and ions. Via these functions, MCS are critical for the survival and the growth of the cell. Owing to that central role in the functioning of cells, MCS dysfunctions lead to important defects of human physiology, influence viral and bacterial infection, and cause disease such as inflammation, type II diabetes, neurodegenerative disorders, and cancer. To approach such a multifaceted topic, this volume assembles a series of chapters dealing with the full array of research about MCS and their respective roles for diseases. Most chapters also introduce the history and the state of the art of MCS research, which will initiate discussion points for the respective types of MCS for years to come. This work will appeal to all cell biologists as well as researchers on diseases that are impacted by MCS dysfunction. Additionally, it will stimulate graduate students and postdocs who will energize, drive, and develop the research field in the near future.
