Download or read book Alzheimer s Disease written by Philippe Derreumaux and published by World Scientific. This book was released on 2013 with total page 465 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease is the most common form of senile dementia, affecting more than 24 million people worldwide. It is characterised pathologically by abnormally high levels of brain lesions in dead and dying neurons, and by elevated numbers of amyloid deposits in the walls of cerebral blood vessels. This book provides a panoramic view across recent in vitro and in vivo studies along with state-of-the-art computer simulations, designed to increase the readers' understanding of oligomerisation and fibril formation.
Download or read book Alzheimer s Disease Insights Into Low Molecular Weight And Cytotoxic Aggregates From In Vitro And Computer Experiments Molecular Basis Of Amyloid beta Protein Aggregation And Fibril Formation written by Philippe Derreumaux and published by World Scientific. This book was released on 2012-12-31 with total page 465 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease is the most common form of senile dementia, affecting more than 24 million people worldwide. It is characterised pathologically by abnormally high levels of neurofibrillary tangles resulting from the accumulation of tau protein in dead and dying neurons, and by elevated numbers of senile plaques in the cortex and hippocampus of the brain. The major component of senile plaques is a small protein of 39-43 amino acids called amyloid-β (Aβ). Thus far, no treatment has been shown to slow the progression of sporadic and familial Alzheimer's disease.A large body of evidence points, however, to the early Aβ-formed oligomers as the primary toxic species in Alzheimer's disease. A powerful strategy for developing pharmaceutical treatments against Alzheimer's is to elucidate the pathways of oligomer formation and determine the structures of the toxic aggregates.This book provides a panoramic view across recent in vitro and in vivo studies along with state-of-the-art computer simulations, designed to increase the readers' understanding of Aβ oligomerisation and fibril formation. At the same time, the book delves into the pathogenesis of familial and sporadic Alzheimer's disease at the atomic level of detail.Written by leading authors in their respective fields, this book will be valuable to all scientists working on Alzheimer's disease./a
Download or read book Protein Aggregation and Fibrillogenesis in Cerebral and Systemic Amyloid Disease written by J. Robin Harris and published by Springer Science & Business Media. This book was released on 2012-12-09 with total page 654 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume of the Subcellular Biochemistry series is the result of the long-standing research interest of the editor in the molecular mechanism underlying Alzheimer’s disease and other amyloid diseases, indicated also by the earlier book in the series (Volume 38), devoted to Alzheimer’s disease. The broad coverage within the present amyloidogenesis book represents an attempt to collate current knowledge relating to the proteins and peptides involved in most of the known amyloid diseases, together with some amyloid/fibril-forming proteins and peptides that are not involved in diseases. Thus, the range of topics included is comprehensive and furthermore it was thought appropriate to include both basic science and clinical presentation of the subjects under discussion.
Download or read book Alzheimer s Disease Cellular and Molecular Aspects of Amyloid beta written by J. Robin Harris and published by Springer Science & Business Media. This book was released on 2006-11-22 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: To understand Alzheimer's disease (AD) is one of the major thrusts of present-day clinical research, strongly supported by more fimdamental cellular, biochemical, immunological and structural studies. It is these latter that receive attention within this book. This compilation of 20 chapters indicates the diversity of work currently in progress and summarizes the current state of knowledge. Experienced authors who are scientifically active in their fields of study have been selected as contributors to this book, in an attempt to present a reasonably complete survey of the field. Inevitably, some exciting topics for one reason or another have not been included, for which we can only apologize. Standardization of terminology is often a problem in science, not least in the Alzheimer field; editorial effort has been made to achieve standardization between the Chapters, but some minor yet acceptable personal / author variation is still present, i. e. P-amyloid/amyloid-P; Ap42/Apl-42/APi. 42! The book commences with a broad survey of the contribution that the range of available microscopical techniques has made to the study of Alzheimer's amyloid plaques and amyloid fibrillogenesis. This chapter also serves as an Introduction to the book, since several of the topics introduced here are expanded upon in later chapters. Also, it is significant to the presence of this chapter that the initial discovery of brain plaques, by Alois Alzheimer, utilized light microscopy, a technique that continues to be extremely valuable in present-day AD research.
Download or read book Biophysics And Biochemistry Of Protein Aggregation Experimental And Theoretical Studies On Folding Misfolding And Self assembly Of Amyloidogenic Peptides written by Jian-min Yuan and published by World Scientific. This book was released on 2017-06-02 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews current research on the important processes involved in neurodegenerative diseases (e.g. Alzheimer's disease) and the peptides and proteins involved in the amyloidogenic processes. It covers the design and developments of anti-amyloid inhibitors, and gives readers a fundamental understanding of the underlying oligomerization and aggregation processes of these diseases from both computational and experimental points of view.
Download or read book Structure and Energetics of Amyloid written by Sarah J. Siegel and published by . This book was released on 2008 with total page 366 pages. Available in PDF, EPUB and Kindle. Book excerpt: The transformation of a soluble protein into an amyloid fibril, a process thought to cause a number of diseases including Alzheimer's disease and Parkinson's disease, is not yet well understood. To discover new therapeutic strategies for these diseases, it is important to understand the process by which these proteins aggregate and cause disease. The actual structures of the aggregates formed during in vitro aggregation experiments of disease-related amyloid proteins depend strongly on the misassembly conditions. A frustrated folding energy landscape describes a system in which changes in environmental conditions dramatically affect the free energy landscape and thus the morphology of aggregate formed. Because proteins associated with pathology did not evolve their sequences to adopt amyloid structures, these proteins could have more frustrated energy landscapes for amyloid formation than those of evolved monomer folds or evolved functional amyloidogenic proteins. A[beta] 1-40, whose aggregation is associated with Alzheimer's disease, reacts with the oxidative metabolite 4-hydroxynonenal. This aberrant post-translational modification covalently cross-links A[beta] 1-40 peptides, causing A[beta] 1-40 to aggregate more quickly into protofibrils and eventually into long, curly fibrils. While enhancing aggregation, the Schiff base and/or Michael reactions between A[beta] 1-40 and 4-hydroxynonenal prevent the formation of long, straight fibrils. Not only is this apparently relevant to disease onset, as 4-hydroxynonenal is found at elevated levels in Alzheimer's patients as compared to age-matched controls and is detected in A[beta] plaques, but it also indicates a frustrated folding energy landscape for A[beta] amyloid, where the addition of a small molecule can change the quaternary structure of aggregates formed. This change in aggregate structure may lead to a more toxic conformation that induces sporadic Alzheimer's disease. [alpha]-Synuclein, associated with Parkinson's disease, also shows signs of frustration in its amyloid formation reaction. Upon the addition of 3 M guanidine hydrochloride, [alpha]-synuclein fibrils convert into an alternate structure with differences in their morphology, surface properties, protease resistance, and pattern of exchange with solvent that indicates a different molecular packing of monomer within the fibril. That different structures are populated under different amyloidogenesis conditions indicates that there are multiple accessible quaternary structures of similar energy that these pathological amyloid proteins can adopt, as expected when aggregation is governed by a frustrated energy landscape. Unlike pathological amyloid proteins, native amyloid proteins require an amyloid quaternary structure to carry out their function, suggesting that they evolved their sequences to form an amyloid structure that is stable to changes in the environment. Therefore, we hypothesize that native amyloid exhibits a funneled folding energy landscape comparable to that of a globular folded protein, unlike the rough aggregation energy landscapes exhibited by pathological amyloidogenesis. We compared the aggregation of [alpha]-synuclein and CsgA, the latter of which is a native amyloid, and found that CsgA aggregates more quickly, forms larger associations of fibrils, and exhibits higher fibril stability in denaturant than [alpha]-synuclein. These properties seem to logically support CsgA's role in biofilm formation, and the hypothesis that CsgA may have evolved specifically for this purpose. [alpha]-Synuclein, which does not function in an amyloid structure as far as we know, had no evolutionary imperative to evolve its primary structure for robust amyloidogenesis characteristics. We suggest that pathological amyloid proteins have rough or frustrated energy landscapes, and that since native amyloid proteins appear to have evolved to form amyloid, they likely have smoother, funneled energy landscapes. This affects how we think about and manipulate the process of amyloidogenesis for combating disease and utilize the amyloid structure for its material properties.
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 Molecular Mechanism of Amyloid beta Protein Misfolding and the Effects on the Etiopathogenesis of Alzheimer s Disease written by Jessica Wenhua Wu and published by . This book was released on 2011 with total page 118 pages. Available in PDF, EPUB and Kindle. Book excerpt: Amyloid protein misfolding is a central pathological event in a spectrum of human age-related degenerative diseases including Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, tauopathies, and spongiform encephalopathy. These dementias are widespread and affect billions of people worldwide. Although the specific amyloid protein involved in each of these diseases is different, amyloid proteins misfold through a common, conserved pathway to form highly-ordered, beta-sheet-rich fibrillar aggregates. Oligomeric intermediates assembled during this process represent the primary toxic neurotoxic species in many of these diseases. In AD, despite extensive research dedicated to unravel the mechanisms underlying Amyloid beta oligomers' pathological role, the precise mechanisms remain unclear due to lack of detailed structural analysis. In this study, we investigated the causative link between the aberrant structures of protein oligomers and their toxic functions in disease pathogenesis. The data presented here reveal that soluble Amyloid beta oligomers have complex structural polymorphism as evident by the immunological differences between prefibrillar and fibrillar conformations (Chapters Two and Three). Soluble Amyloid beta fibrillar oligomers are rich in beta-sheets, on fibril-forming pathway and can eventually assemble into mature fibrils. In vitro, FOs propagate via an elongation, fragmentation, and replication mechanism that is similar to what is known for prion proteins. We also investigated the molecular mechanisms underlying FOs' pathological role in AD. The increased levels of FOs in AD patients, the tight correlation with the increased severity of dementia, and the structural similarity to fibrils present in amyloid plaques strongly suggest that FOs are highly pathological to AD. Through studies using rat hippocampal and cortical neurons, we found and confirmed that Amyloid beta-mediated neurotoxicity is highly conformation dependent (Chapter Four). In the in vitro cell culture model, FOs induce neuronal toxicity by preferentially binding to a selective-population of stressed neurons at non-synaptic sites through their exposed hydrophobic surface.
Download or read book Structure Aggregation and Inhibition of Alzheimer s Beta amyloid Peptide A Beta written by Qiuming Wang and published by . This book was released on 2013 with total page 193 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease (AD) is the most common age related neurodegenerative disorder pathologically linked with the accumulation of the extracellular senile plaques of [Beta]-Amyloid peptide (A[Beta]) and the intracellular neurofibrillary tangles of tau protein in AD's brains. The deposition of A[Beta] is regarded as the primary causative factor in AD, which involves both neuron cytotoxicity and tau protein hydrophosphorylation. Amyloid formation on the cell membrane involves multiple self-assembly processes in which A[Beta] peptides undergo complex conformational change, aggregation, and reorganization to form characteristic [Beta]-sheet rich fibrils. The kinetics of this self-assembly process and the inhibition of A[Beta] aggregation and toxicity remains an important but open question because of 1) the small size, fast transition, and heterogeneous intermediates of A[Beta] oligomers, 2) complicated surface environment of cell membrane, and 3) no effective pharmaceutical agent was produced to date to treat AD. In this dissertation, both computational and experimental approaches were conducted to (1) investigate the conformation, orientation, and aggregation of amyloid oligomers upon adsorption on artificial surfaces; (2) determine seeding effect of A[Beta] adsorption and kinetic on different artificial surfaces; (3) examine inhibition effect of tanshiones on A[Beta] aggregation and toxicity; (4) explore novel process for A[Beta] inhibitor design. Throughout this week, we for the first time determine the effect of surface chemistry on A[Beta] aggregation and adsorption (Chapter II); and reveal the role of size, conformation, and orientation of A[Beta] oligomer on A[Beta]-surface interaction (Chapter III and Chapter IV). As compared to A[Beta] aggregation in solution, all of the Self-Assembled Monolayers (SAMs) can greatly accelerate A[Beta] aggregation and promote the structural conversion from an unstructured conformation to a [Beta]-sheet-containing structure. Our results suggest that A[Beta] undergoes different aggregation pathways on different SAMs. All these experimental and simulation results represent the first important step towards a better fundamental understanding of amyloid aggregation and toxicity mechanisms at the molecular level. We also discover a type of novel inhibitors of tanshionones from herb extracts which possess multifunction of inhibiting A[Beta] aggregation, disaggregating A[Beta] fibers, and reducing A[Beta]-induced cell toxicity in vitro (Chapter V). Tanshinone-derived compounds constitute a new class of amyloid inhibitors with multiple advantages in amyloid inhibition, fibril disruption, and cell protection, as well as their well-known anti-inflammatory activity, which may hold great promise in treating amyloid diseases. In addition of investigating the naturally existed compounds, a novel technique for the design and identification of amyloidogenic hexapeptide-based A[Beta] inhibitor was developed (Chapter VI). We have suggested a novel hypothesis for the development of hexapeptide-based A[Beta] inhibitors and developed a high-throughput protocol for the design and screen of amyloidogenic hexapeptide sequences as A[Beta] aggregation and cytotoxicity inhibitors. The successful identification of A[Beta] inhibitors through this work highly confirmed that analyzing the self-recognition short peptide fragments is a promising strategy for developing peptide-based inhibitors of Alzheimer's disease. And the common concept of cross-amylid interaction could also potentially be used to the identification of inhibitors for other amyloid diseases. The self-recognition hexapeptide fragments designed in QSAR model, in together with the high throughput MD simulation model, can be widely used for amyloidosis mechanism study and amyloid inhibitor screen.
Download or read book Role of Transformation in Modulating beta amyloid Aggregation and Toxicity written by Lin Liu and published by . This book was released on 2007 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structural and Biochemical Studies of Patient extracted Amyloid Fibrils written by Yi Xiao Jiang and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human neurodegenerative diseases cause the gradual loss of neurons and progressive decline in memory, cognitive ability, movement and behavior. These devastating conditions afflict millions of patients worldwide and their families, however the molecular mechanisms of pathogenesis are not well understood, resulting in the lack of effective treatments and early diagnostic tools. Gross analyses of post-mortem brains using immunohistochemistry has identified abnormal deposits of amyloid proteins as defining features of neurodegenerative diseases. Amyloid proteins, like prions, can template aggregation of monomers into highly ordered, stable fibrils composed of tightly interdigitating [Beta]-sheets. Recent advances in cryogenic-electron microscopy (cryo-EM) have enabled the structural determination of amyloid fibrils to near-atomic resolution. These structures provide insight into the formation and propagation of amyloid fibrils, and can guide the design of therapies that prevent, delay, or reverse the aggregation of proteins in neurodegenerative diseases. Moreover, previous work has shown that the structures of brain-extracted fibrils differ from the structures of fibrils assembled in vitro, underscoring the importance of studying patient-derived samples. In my thesis research, I extracted amyloid fibrils from autopsied brains of patients with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and determined their structures using cryo-EM. Surprisingly, the fibrils examined were not formed by TDP-43 but by a fragment of transmembrane protein 106B (TMEM106B), revealing a previously unsuspected amyloid protein. In addition, I used a biosensor cell line, which detects proteopathic TDP-43 aggregates from sarkosyl-insoluble brains extracts, to study cohorts of TDP-43 proteinopathy cases including amyotrophic lateral sclerosis (ALS), FTLD-TDP and Alzheimer's disease (AD). My work expands the insight into the molecular basis of amyloid disorders, and inspires future research to address newly raised questions about TMEM106B and TDP-43 in neurodegenerative diseases.
Download or read book Alzheimer Amyloid Peptide Aggregation Alternate Products of Fibril Formation written by Tze-Hsien Jackson Huang and published by . This book was released on 2001 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: In Alzheimer disease (AD), polymerization of the amyloid ß peptide (Aß) to form fibrillar deposits in the brain is associated with neurodegeneration. Because of this, researchers have worked to understand fibrillogenesis and the toxicity of fibrils. However, recent discoveries suggest intermediate structures in Aß fibril formation are also toxic. We sought to gain a better understanding of intermediate structures in the fibrillogenesis pathway, describe conditions where Aß forms biologically inert amorphous amyloid rather than neurotoxic fibrillar amyloid, and elucidate some of the extrinsic factors controlling conversion of Aß monomers to fibrils. At low micromolar concentrations, Aß40, the 40 residue form of Aß, assembled into two types of soluble oligomers depending upon pH. Dimer/tetramers with irregular secondary structure formed at neutral pH while spherical particles with a mass of 0.94 megadaltons and ß-sheet secondary structure formed at pH 3. Both structures were stable for at least 4 weeks; this stability will allow for further investigation using high-resolution techniques. In the laboratory, Aß often precipitates to form non-specific aggregates. We sought to characterize these aggregates for use as an 'in vitro ' model for amorphous amyloid. These aggregates were ß-structured at peptide concentrations >10 [mu]M and unfolded at lower concentrations. The structured aggregates were tightly packed containing peptides inaccessible to water. Peptides in the unstructured aggregates were loosely packed, mobile and accessible to water. Structured aggregates appeared protofibrillar and developed into mature fibrils after several weeks whereas the unstructured aggregates were invisible by EM and did not generate fibrils. These findings suggest the unstructured aggregates share many properties with the amorphous amyloid of AD and may aid in studying amorphous amyloid 'in vitro'. We used the organic osmolytes trimethylamine 'N'-oxide (TMAO) and glycerol as mimics of naturally occurring chaperone molecules to investigate their effects upon fibrillogenesis. TMAO and glycerol accelerated the Aß random coil to ß-sheet conformational change. This transition occurred with the immediate conversion of amorphous unstructured aggregates to uniform globular structures. TMAO and glycerol also mediated the transformation of protofibrils to mature fibrils. Thus, the effects of extrinsic factors such as chaperone molecules must be considered when studying Aß fibrillogenesis.
Download or read book The Biology of Alzheimer Disease written by Dennis J. Selkoe and published by Cold Spring Harbor Perspective. This book was released on 2012 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer disease causes the gradual deterioration of cognitive function, including severe memory loss and impairments in abstraction and reasoning. Understanding the complex changes that occur in the brain as the disease progressesincluding the accumulation of amyloid plaques and neurofibrillary tanglesis critical for the development of successful therapeutic approaches. Written and edited by leading experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine includes contributions covering all aspects of Alzheimer disease, from our current molecular understanding to therapeutic agents that could be used to treat and, ultimately, prevent it. Contributors discuss the biochemistry and cell biology of amyloid -protein precursor (APP), tau, presenilin, -secretase, and apolipoprotein E and their involvement in Alzheimer disease. They also review the clinical, neuropathological, imaging, and biomarker phenotypes of the disease; genetic alterations associated with the disorder; and epidemiological insights into its causation and pathogenesis. This comprehensive volume, which includes discussions of therapeutic strategies that are currently used or under development, is a vital reference for neurobiologists, cell biologists, pathologists, and other scientists pursuing the biological basis of Alzheimer disease, as well as investigators, clinicians, and students interested in its pathogenesis, treatment, and prevention.
Download or read book Modulation of Alzheimer s Disease Amyloid Beta Peptide Aggregation by Molecular Chaperones Polyphosphates and Metal Ions and Their Interplay written by Sara Maria Ayala Mariscal and published by . This book was released on 2018 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease is the most frequent type of dementia. With an exponentially growing number of cases, understanding the underlying molecular events leading to this devastating condition is of crucial importance. Much evidence points to a disequilibrium in the production and degradation of amyloid beta (Aß), a normally physiological 42 amino acid peptide, as an early key event in Alzheimer's etiology. Whether Aß is overproduced or poorly degraded, the overall result is an abnormally large pool of peptide that gradually aggregates forming extracellular deposits of fibrils, called amyloid plaques, in specific brain regions. Hence, modulation of Aß aggregation process is one of the suggested approaches to control the evolution of Alzheimer's disease. Universally conserved molecular chaperones have been intensively studied for their capacity to prevent aggregation of disease-related proteins, and many of them have proven to efficiently modulate Alzheimer's Aß aggregation. In a scenario where chaperones are overexpressed or directly administered into the affected tissue, the universal conservation and the relatively poor client-specificity of generic chaperones can become a downside because of the risk of interaction with proteins other than the targeted one is not dismissible, and thus the consequences unpredictable. In the first part of this work, we looked upon a bacterial chaperone call SecB with an unusually robust holdase activity (i.e. it prevents early protein folding) as a promising modulator of Alzheimer's Aß peptide aggregation. [...].
Download or read book The Effect of Osaka Mutation on Oligomer Formation of Full Length Amyloid beta Protein Oligomers written by Riya Shah and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease (AD) is the leading cause of dementia among the elderly and is characterized by loss of memory due to neuronal death. In vitro and in vivo experiments have identified soluble, low-molecular weight, non-covalently bonded oligomeric forms of amyloid [beta]-protein (A) as the likely toxic species that leads to AD. The Osaka mutation ([E22[delta]]), discovered in a Japanese family, is associated with an early-onset AD in the carriers of this mutation, and involves a deletion of the glutamic acid at the twenty-second position in A[beta]. A[beta] with Osaka mutation can be used to probe the effect of singular deletions on oligomerization and protein conformations. We use discrete molecular dynamics (DMD) simulations with a four-bead protein model and implicit solvent to study the oligomerization of the two most predominant alloforms, A[beta]1-40 and A[beta]1-42, and their Osaka mutants. Our findings suggest that the Osaka mutation alters A[beta]1-40 structure and assembly mechanics to be more similar to A[beta]1-42 and [E22[delta]]A[beta]1-42. Specifically, the Osaka mutation greatly affects the secondary structure of A[beta]1-40 in the N-terminal region to make it resemble A[beta]1-42. We also show that [E22[delta]]A[beta]1-40 and [E22[delta]]A[beta]1-42 tend to assemble into larger oligomers than their wild-type (WT) counterparts and that both mutants are more prone than wild type A[beta] to forming a tertiary contact between D23 and K28. The proximity of negatively charged D23 and positively charged K28 is expected to induce an intrapeptide salt bridge, stabilization of which is known for speeding up fibril formation. These results provide a plausible explanation of why Osaka mutants aggregate into fibrils much faster than WT peptides. The early-onset properties of the Osaka mutation might be attributed to the resemblance of [E22[delta]]A[beta]1-40 oligomer conformations to those formed by A[beta]1-42, specifically the property of A[beta]1-42 possessing disordered and solvent accessible N-termini, which would readily interact with and potentially disrupt cellular membranes.
Download or read book Effects of Low Molecular Weight Glycosaminoglycans in Amyloid Beta induced Models of Alzheimer s Disease written by Mark A. Walzer and published by . This book was released on 2003 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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”.
