Download or read book Characterization of Novel Amyloid beta Peptide A beta Binding Ligands written by Silke Dornieden and published by Forschungszentrum Jülich. This book was released on 2012 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of Toxic Abeta Oligomers ADDLs Amyloid beta derived Diffusible Ligands written by Brett A. Chromy and published by . This book was released on 2001 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease is a neurodegenerative disorder that afflicts over 25 million people worldwide and currently has no cure. The amyloid beta peptide (Abeta) is believed to be causative in the disease, but the exact form of the peptide responsible is unknown. The prevailing theory for Abeta toxicity is that innocuous monomer must reorganize into larger structures and form fibrils in order to be toxic. Recently, pre-fibrillar forms of the peptide have been discovered and are gaining in prominence as possible critical toxic structural species. We have discovered one of these pre-fibrillar forms of amyloid beta and have named them, ADDLs (Amyloid-beta-derived diffusible ligands). These structures are individual, globular, oligomeric species and are structurally distinct from other pre-fibrillar structures, such as rings, protofibrils, or micelles. We have designed several polyclonal antibodies to investigate these oligomers. Atomic force microscopy (AFM) and gel electrophoresis techniques have established the structure of the molecules. ADDLs have been demonstrated to block LTP, a model for learning and memory. It may be through this process that ADDLs exert their effect on the human brain and elicit the symptoms of AD. Moreover, the LTP and toxic effects of ADDLs are dependent upon the presence of Fyn, a Src-family tyrosine kinase, shown to be upregulated in AD. We have generated Fyn containing cell lines to examine the effects of Fyn more closely. Fyn has also been shown to phosphorylate tau, which is the main component of the other 'hallmark' of AD, the presence of paired helical filaments (PHFs) inside neurons of AD-afflicted brains. Although ADDLs have not been shown to conclusively elicit apoptosis, we have shown that perturbations in the microtubule network induce neuronal apoptosis through an unknown tyrosine kinase, possibly involving the Fyn-dependent signal transduction mechanism used by ADDLs. Apoptosis may play a role in how neurons die in AD, and disruption of the microtubule system through protein tyrosine phosphorylation may play a role in the apoptosis. ADDLs, Fyn, and protein tyrosine phosphorylation may represent central aspects of the cause of AD and further examination of these topics may eventually lead to a cure for this devastating disease.
Download or read book Mechanisms of Cell Toxicity written by E. Edward Bittar and published by JAI Press(NY). This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular toxicology has entered a new era. No longer are we concerned only with necrotic cell death produced by severe, acute insult (often to multiple intracellular targets) leading to disruption of the cell membrane. New advances in molecular and cellular biology are allowing the dissection of mechanisms of cell death involving more subtle targets within the cell. Toxicology has been very important, not only in understanding the mechanisms, nature, and severity of toxicity and thereby helping in risk assessment, but toxicology has also played a very important role in helping to understand basic biological processes. Historically this has perhaps been most evident in the use of toxic agents to interfere with specific reactions in the body and hence help to dissect out the mechanisms of metabolic processes. For example, the use of chemical inhibitors was very important in understanding the process of oxidative phosphorylation, or the tricarboxylic acid cycle. More recent examples are seen herein where toxicology interfaces with, for example structural biology in the study of the cytoskeletal components and their interactions. Indirectly, an understanding of the mechanisms of endogenous protective systems also improves knowledge of basic cell biology. Toxic insult and manipulation of cell signalling and control mechanisms in cell growth and differentation also highlight how important the discipline of cell toxicity has been and will continue to be a major contributor to our understanding of basic issues in the biological and biomedical sciences. This book offers selected reviews of some of the principal molecular mechanisms of cell toxicity.
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.
Download or read book Handbook of Neurochemistry and Molecular Neurobiology written by Abel Lajtha and published by Springer Science & Business Media. This book was released on 2008-06-06 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: The nervous system is highly fragile, especially during aging, illness and trauma. This book addresses a small sampling of major constituents of neural function at the cellular and molecular level that play crucial roles in development and aging.
Download or read book Amyloid Proteins written by Einar M. Sigurdsson and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt: A proven collection of readily reproducible techniques for studying amyloid proteins and their involvement in the etiology, pathogenesis, diagnosis, and therapy of amyloid diseases. The contributors provide methods for the preparation of amyloid and its precursors (oligomers and protofibrils), in vitro assays and analytical techniques for their study, and cell culture models and assays for the production of amyloid proteins. Additional chapters present readily reproducible techniques for amyloid extraction from tissue, its detection in vitro and in vivo, as well as nontransgenic methods for developing amyloid mouse models. The protocols follow the successful Methods in Molecular BiologyTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.
Download or read book Animal Models of Cognitive Impairment written by Edward D. Levin and published by CRC Press. This book was released on 2006-06-22 with total page 395 pages. Available in PDF, EPUB and Kindle. Book excerpt: The costs associated with a drug's clinical trials are so significant that it has become necessary to validate both its safety and efficacy in animal models prior to the continued study of the drug in humans. Featuring contributions from distinguished researchers in the field of cognitive therapy research, Animal Models of Cognitive Impairmen
Download or read book Rapid Development of Small molecule Producing Microorganisms Based on Metabolite Sensors written by Stephan Binder and published by Forschungszentrum Jülich. This book was released on 2013 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Protein Self Assembly written by Jennifer J. McManus and published by Humana. This book was released on 2020-08-08 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores experimental and computational approaches to measuring the most widely studied protein assemblies, including condensed liquid phases, aggregates, and crystals. The chapters in this book are organized into three parts: Part One looks at the techniques used to measure protein-protein interactions and equilibrium protein phases in dilute and concentrated protein solutions; Part Two describes methods to measure kinetics of aggregation and to characterize the assembled state; and Part Three details several different computational approaches that are currently used to help researchers understand protein self-assembly. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Protein Self-Assembly: Methods and Protocols is a valuable resource for researchers who are interested in learning more about this developing field.
Download or read book Bio nanoimaging written by Vladimir N Uversky and published by Academic Press. This book was released on 2013-11-05 with total page 556 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering: - Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits - Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers - Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme aggregation, misfolded intermediate of a PDZ domain, and micelle formation by human islet amyloid polypeptide Protein misfolding and aggregation is a fast-growing frontier in molecular medicine and protein chemistry. Related disorders include cataracts, arthritis, cystic fibrosis, late-onset diabetes mellitus, and numerous neurodegenerative diseases like Alzheimer's and Parkinson's. Nanoimaging technology has proved crucial in understanding protein-misfolding pathologies and in potential drug design aimed at the inhibition or reversal of protein aggregation. Using these technologies, researchers can monitor the aggregation process, visualize protein aggregates and analyze their properties. Provides practical examples of nanoimaging research from leading molecular biology, cell biology, protein chemistry, biotechnology, genetics, and pharmaceutical labs Includes over 200 color images to illustrate the power of various nanoimaging technologies Focuses on nanoimaging techniques applied to protein misfolding and aggregation in molecular medicine
Download or read book Tau oligomers written by Jesus Avila and published by Frontiers E-books. This book was released on 2014-08-18 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer’s Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a “toxic” form of tau protein. Moreover, it was suggested that a “toxic” tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, “tau oligomers” as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of “tau oligomers”.
Download or read book Alzheimer s Disease Drug Development written by Jeffrey Cummings and published by Cambridge University Press. This book was released on 2022-03-31 with total page 575 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides a definitive overview of the complex ecosystem facilitating Alzheimer's Disease drug research and development. Demonstrates a drug's journey from in the lab, clinical trial testing, regulatory review, and marketing by pharmaceutical companies. Details the use of artificial intelligence, clinical trial management, and financing models.
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.
Download or read book Apolipoprotein E and Alzheimer s Disease written by A.D. Roses and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is now considerable genetic evidence that the type 4 allele of the apolipoprotein E gene is a major susceptibility factor associated with late-onset Alzheimer's disease, the common form of the disease defined as starting after sixty years of age. The role of apolipoprotein E in normal brain metabolism and in the pathogenesis of Alzheimer's disease are new and exciting avenues of research. This book, written by the most outstanding scientists in this new filed, is the first presentation of results concerning the implications of apolipoprotein E on the genetics, cell biology, neuropathology, biochemistry, and therapeutic management of Alzheimer's disease.
Download or read book Pathobiology of Alzheimer s Disease written by and published by Elsevier. This book was released on 1995-10-17 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences. Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas. The last decade has seen tremendous advances in our understanding of the pathobiology of Alzheimer's disease. These will lead to the first generation of drugs aimed at prevention rather than cure. This book covers some of the most important and exciting of these advances, with chapters written by many of the leading researchers in the field. With genetic studies as a backbone to this volume many chapters are devoted to the function and regulation of amyloid b-protein precursor (APP) and apolipoprotein E (ApoE). Other chapters describe cell biological approaches helping to piece together the link between the genetic alterations and the phenotype we call Alzheimer's disease. Although APP and its proteolytic cleavage product, amyloid b-protein, do not answer all the questions, detailed research into this system has undoubtedly increased our knowledge of the pathobiology of AD and has lead to the identification of other risk factors. Understanding the role of ApoE in the pathology of Alzheimer's disease promises to open a whole new field in AD research. * * Reviews the current knowledge of the pathogenesis of Alzheimer's Disease from a clinical perspective to a genetic and cell biological perspective * A comprehensive description of the role of amyloid B-protein precursor in Alzheimer's disease. * Up-to-date research data * Clear illustrations complement the text
Download or read book Biological Soft Matter written by Corinne Nardin and published by John Wiley & Sons. This book was released on 2021-04-06 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biological Soft Matter Explore a comprehensive, one-stop reference on biological soft matter written and edited by leading voices in the field Biological Soft Matter: Fundamentals, Properties and Applications delivers a unique and indispensable compilation of up-to-date knowledge and material on biological soft matter. The book presents a thorough overview about biological soft matter, beginning with different substance classes, including proteins, nucleic acids, lipids, and polysaccharides. It goes on to describe a variety of superstructures and aggregated and how they are formed by self-assembly processes like protein folding or crystallization. The distinguished editors have included materials with a special emphasis on macromolecular assembly, including how it applies to lipid membranes, and proteins fibrillization. Biological Soft Matter is a crucial resource for anyone working in the field, compiling information about all important substance classes and their respective roles in forming superstructures. The book is ideal for beginners and experts alike and makes the perfect guide for chemists, physicists, and life scientists with an interest in the area. Readers will also benefit from the inclusion of: An introduction to DNA nano-engineering and DNA-driven nanoparticle assembly Explorations of polysaccharides and glycoproteins, engineered biopolymers, and engineered hydrogels Discussions of macromolecular assemblies, including liquid membranes and small molecule inhibitors for amyloid aggregation A treatment of inorganic nanomaterials as promoters and inhibitors of amyloid fibril formation An examination of a wide variety of natural and artificial polymers Perfect for materials scientists, biochemists, polymer chemists, and protein chemists, Biological Soft Matter: Fundamentals, Properties and Applications will also earn a place in the libraries of biophysicists and physical chemists seeking a one-stop reference summarizing the rapidly evolving topic of biological soft matter.
Download or read book Handbook of In Vivo Chemistry in Mice written by Katsunori Tanaka and published by John Wiley & Sons. This book was released on 2020-04-27 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides timely, comprehensive coverage of in vivo chemical reactions within live animals This handbook summarizes the interdisciplinary expertise of both chemists and biologists performing in vivo chemical reactions within live animals. By comparing and contrasting currently available chemical and biological techniques, it serves not just as a collection of the pioneering work done in animal-based studies, but also as a technical guide to help readers decide which tools are suitable and best for their experimental needs. The Handbook of In Vivo Chemistry in Mice: From Lab to Living System introduces readers to general information about live animal experiments and detection methods commonly used for these animal models. It focuses on chemistry-based techniques to develop selective in vivo targeting methodologies, as well as strategies for in vivo chemistry and drug release. Topics include: currently available mouse models; biocompatible fluorophores; radionuclides for radiodiagnosis/radiotherapy; live animal imaging techniques such as positron emission tomography (PET) imaging; magnetic resonance imaging (MRI); ultrasound imaging; hybrid imaging; biocompatible chemical reactions; ligand-directed nucleophilic substitution chemistry; biorthogonal prodrug release strategies; and various selective targeting strategies for live animals. -Completely covers current techniques of in vivo chemistry performed in live animals -Describes general information about commonly used live animal experiments and detection methods -Focuses on chemistry-based techniques to develop selective in vivo targeting methodologies, as well as strategies for in vivo chemistry and drug release -Places emphasis on material properties required for the development of appropriate compounds to be used for imaging and therapeutic purposes in preclinical applications Handbook of In Vivo Chemistry in Mice: From Lab to Living System will be of great interest to pharmaceutical chemists, life scientists, and organic chemists. It will also appeal to those working in the pharmaceutical and biotechnology industries.
