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Methods in Tau Cell Biology, Volume 141, the latest release in the Methods in Cell Biology series, looks at methods involved in tau cell biology. Edited by leaders in the field, this volume provides proven, state-of-art techniques and relevant historical background and theory that aids researchers with tactics for efficient design and effective implementation of experimental methodologies. Topics of note in this updated volume include sections on Recombinant tau expression and purification, In vitro MT dynamics and MT ends, Methods related to investigating tau structure and MT bundling, Neurite outgrowth and retraction, and Methods related to studying tau fragmentation. Covers sections on Tau Cell Biology Written by experts in the field of cell biology Includes cutting-edge materials
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”.
This detailed volume gathers basic and advanced methods and protocols from in vitro assays and in vivo models to address the molecular and functional aspects of tau physiopathology. Divided into five parts that illustrate the underlying molecular mechanisms of Tau functions and dysfunctions in Alzheimer’s disease and other dementia referred to as tauopathies, this volume discusses timely topics such as: conformational studies of native tau protein and investigation of its physiological function in microtubules binding and tubulin polymerization; in vitro methods of formation and detection of tau oligomers and PHF-like fibrils; characterization and in vitro introduction of post-translational modifications on tau proteins for further functional studies; analytical tools for the detection of tau proteins, their modifications and cellular interactions, and MAPT gene mutations in various biological samples; and cellular and in vivo models for the investigations of tau physiopathology. 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. Practical and cutting-edge, Tau Protein: Methods and Protocols is a valuable resource that addresses the most recent aspects of Alzheimer’s disease research related to Tau protein and state-of-the-art experimental techniques. It targets a broad scientific audience including molecular biologists and biochemists, as well as all researchers interested in exploring the functions of tau proteins.
This book presents essential studies and cutting-edge research results on tau, which is attracting increasing interest as a target for the treatment of Alzheimer's disease. Tau is well known as a microtubule-associated protein that is predominantly localized in the axons of neurons. In various forms of brain disease, neuronal loss occurs, with deposition of hyperphosphorylated tau in the remaining neurons. Important questions remain regarding the way in which tau forms hyperphosphorylated and fibrillar deposits in neurons, and whether tau aggregation represents the toxic pathway leading to neuronal death. With the help of new technologies, researchers are now solving these long-standing questions. In this book, readers will find the latest expert knowledge on all aspects of tau biology, including the structure and role of the tau molecule, tau localization and function, the pathology, drivers, and markers of tauopathies, tau aggregation, and treatments targeting tau. Tau Biology will be an invaluable source of information and fresh ideas for those involved in the development of more effective therapies and for all who seek a better understanding of the biology of the aging brain.
Some well-known age-related neurological diseases include Parkinson's disease, Alzheimer's disease, deafness, and blindness. Even more common are the problems of aging which are not due to disease but to more subtle impairments in neurobiological systems, including impairments in vision, memory loss, muscle weakening, and loss of reproductive functions, changes in body weight, and sleeplessness. As the average age of our society increases, diseases of aging continue to become more common, and conditions associated with aging need more attention by doctors and researchers. In 1991, patients over the age of 65 saw their doctors an average of eight times per year. Research funding is provided by the Neuroscience and Neuropsychology of Aging (NNA) Program, which is run by the National Institute on Aging. This book offers a comprehensive overview of all topics related to functional impairments which are related to the aging brain and nervous system. It is organized according to four general functions: movement, senses, memory, and neuroendocrine regulation. Written by the leading researchers in the field, this comprehensive work addresses both impairments associated with diseases and not associated with diseases, making it easier to understand the mechanisms involved. Functional Neurobiology of Aging is an important reference for professionals and students involved in aging research, as well as physicians who need to recognize and understand age-related impairments. - Organized by function, making it easy to find and understand the material - Addresses impairments both associated with diseases and not associated with diseases - Written by leading researchers in the field - Most comprehensive source of information on the neurobiology of aging
Covering the major classes of posttranslational modifications, Posttranslational Modification of Proteins is the first comprehensive treatment of this burgeoning area of proteome diversification.
Genes, Environment and Alzheimer's Disease discusses the role that activities such as exercise can play in cardiovascular health, while also highlighting the fact that the last 10 years have brought great discoveries in the strong environmental component of brain disorders, neurodegeneration, and cognitive decline. It is now clear that brain insult is an environmental risk factor for AD, while on the other hand, lifestyle components such as exercise and level of education may play a protective role, delaying the onset and/or severity of the disease. Evidence from experiments in rodent models of Alzheimer's disease contributes major insight into the molecular mechanisms by which the environment plays its role in AD. Additionally, there are diseases related to lifestyle that may lead to AD. This volume reviews new discoveries related to all these factors, serving as a translational tool for clinicians and researchers interested in genetic and environmental risk factors for the disease. - Provides the first volume to link genetic and environmental risk factors for Alzheimer's disease and dementia - Aids researchers and clinicians in understanding the basic mechanisms of Alzheimer's disease and cognitive decline - Brings the basic science and clinical perspectives together in a single volume, facilitating translational possibilities - Includes a range of molecular to behavioral components assembled into a single volume that creates an excellent resource for basic and clinical neuroscientists
Computational methods are playing an ever increasing role in cell biology. This volume of Methods in Cell Biology focuses on Computational Methods in Cell Biology and consists of two parts: (1) data extraction and analysis to distill models and mechanisms, and (2) developing and simulating models to make predictions and testable hypotheses. Focuses on computational methods in cell biology Split into 2 parts--data extraction and analysis to distill models and mechanisms, and developing and simulating models to make predictions and testable hypotheses Emphasizes the intimate and necessary connection with interpreting experimental data and proposing the next hypothesis and experiment
This second edition volume details the latest aspects of neural cells covering the practical and theoretical considerations of each techniques involved. Chapters guide readers through a general overview of the neuronal culturing principles, cell line models for neural cells, the isolation and propagation of primary cultures, stem cells, transfection and transduction of neural cultures, and other more advanced techniques. 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. Practical and easy to use, Neuronal Cell Culture: Methods and Protocols, Second Edition aims to be of interest to scientists at all levels studying cell culture models for neuroscientific studies.
After years of hard work, Dr. Charly McKenna finally has it all. Prosperous career as a dermatologist? Check. Spacious apartment overlooking Central Park? Check. Handsome lawyer husband? Double check.Then one night, a bullet rips through the right side of her skull and she loses everything.As Charly struggles to recover from her brain injury, she begins to realize that the events of that fateful night are trapped in the damaged right side of her brain. Now she must put the jigsaw pieces together to discover the identity of the man who tried to kill her... before he finishes the job he started.