Tau Oligomers

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.

The 1st World Congress on Geriatrics and Neurodegenerative Disease Research (GeNeDis 2014), will focus on recent advances in geriatrics and neurodegeneration, ranging from basic science to clinical and pharmaceutical developments and will provide an international forum for the latest scientific discoveries, medical practices and care initiatives. Advances information technologies will be discussed along with their implications for various research, implementation and policy concerns. In addition, the conference will address European and global issues in the funding of long-term care and medico-social policies regarding elderly people. GeNeDis 2014 takes place in Corfu, Greece, 10-13 April 2014. This volume focuses on the sessions that address neurodegenerative diseases.

A Paradigm Shift to Prevent and Treat Alzheimer’s Disease: From Monotargeting Pharmaceuticals to Pleiotropic Plant Polyphenols is the first book to systematically exhibit the powerful pleiotropic pharmacological effects on Alzheimer’s disease of plant-based compounds from ancient foods that humans have been consuming safely with substantial health benefits for thousands of years. These plant-based compounds include curcuminoids from turmeric, resveratrol from red wine and grape seed extract from other grape products, epigallocatechin-gallate (EGCG) from green tea, and oleocanthal and oleuropein from olive oil, in addition to a special extract, EGb 761, from the leaves of Ginkgo biloba, the oldest living species of tree on earth. This book also presents a new analytical framework that convincingly favors a multi-targeting ("pleiotropic") approach to the prevention and treatment of complex chronic diseases, in contrast to the mono-targeting of the pharmaceutical model. A Paradigm Shift to Prevent and Treat Alzheimer’s Disease is a unique and exciting resource for pharmaceutical scientists, pharmacologists, neurologists, general practitioners, research scientists in various medical and life sciences, healthcare professionals in clinical and executive positions, conventional medical schools, schools of naturopathic medicine, healthcare and medical journalists, executives in both national public healthcare systems and private insurers, and informed general readers. Presents carefully compiled evidence supporting the need to shift from pharmaceutical-based mono-targeting to plant polyphenol-based pleiotropic targeting for the prevention and treatment of Alzheimer’s disease Includes valuable tables that aggregate pleiotropic pharmacological effects of the plant polyphenols on Alzheimer’s disease-related pathogenic hallmarks Highlights regulatory aspects and discusses the challenges and potential solutions with respect to bioavailability of certain plant polyphenols

This monograph begins with a general description of the cytoskeleton in axonal development and pathology and then moves to more detailed descriptions of particular components, including microtubules and associated proteins, neurofilaments and interacting proteins, actin and its binding proteins, and glial fibrillary acidic protein. The later chapters focus on the functional significance of the neuronal cytoskeleton in axonal transport and its regulation in health and disease states. The Cytoskeleton of the Nervous System will encourage further development of unifying principles and stimulate new conceptual and technical approaches toward a better understanding of cytoskeleton functions in health and disease.

Alzheimer’s disease is an increasingly common form of dementia and despite rising interest in discovery of novel treatments and investigation into aetiology, there are no currently approved treatments that directly tackle the causes of the condition. Due to its multifactorial pathogenesis, current treatments are directed against symptoms and even precise diagnosis remains difficult as the majority of cases are diagnosed symptomatically and usually confirmed only by autopsy. Alzheimer’s Disease: Recent Findings in Pathophysiology, Diagnostic and Therapeutic Modalities provides a comprehensive overview from aetiology and neurochemistry to diagnosis, evaluation and management of Alzheimer's disease, and latest therapeutic approaches. Intended to provide an introduction to all aspects of the disease and latest developments, this book is ideal for students, postgraduates and researchers in neurochemistry, neurological drug discovery and Alzheimer’s disease.

This book describes the recent advancement of basic research on the biology of aging and longevity studies in various organisms, as well as the neurobiology of aging and neurodegeneration mechanisms. Chapters present new findings and conceptual developments concerning the basic mechanisms of aging and longevity determination. As a follow-up volume to the previous book Aging Mechanisms (2015), it overviews the rapid progress of aging research introducing new topics from leading laboratories in Japan. Chapter contributors are selected based on recent scientific achievements on the mechanisms of aging in various model organisms, including yeast, worm (C. elegans), fly (Drosophila), mice, and rats. Chapters are ordered from the discussion on molecular and cellular levels to physiological and systemic levels. The book also provides an overview of aging science in the region and helps readers quickly grasp who is doing what in this research area. As the aging of population becomes an ever more pressing issue in Asia, advancing the understanding of basic mechanisms of organism aging and longevity determination will be crucial to developing more effective therapies and protective strategies. Researchers and graduate students in biomedical aging research will find this as a rich source of information and a stimulus to novel research directions.