Development Of A Human Cell Model Of Amyloid Seeding And Aggregation To Investigate Alzheimer S Disease Pathology
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Development Of A Human Cell Model Of Amyloid Seeding And Aggregation To Investigate Alzheimer S Disease Pathology
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Author : Ludmila Martinova Sheytanova
language : en
Publisher:
Release Date : 2018
Development Of A Human Cell Model Of Amyloid Seeding And Aggregation To Investigate Alzheimer S Disease Pathology written by Ludmila Martinova Sheytanova and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
Protein Aggregation And Fibrillogenesis In Cerebral And Systemic Amyloid Disease
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Author : J. Robin Harris
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-09
Protein Aggregation And Fibrillogenesis In Cerebral And Systemic Amyloid Disease written by J. Robin Harris and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-09 with Medical categories.
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.
Amyloid Protein Precursor In Development Aging And Alzheimer S Disease
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Author : C.L. Masters
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-04-17
Amyloid Protein Precursor In Development Aging And Alzheimer S Disease written by C.L. Masters and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-04-17 with Science categories.
This book summarizes the last ten years' research on Alzheimer's disease. Genetic mutations in the gene which codes for amyloid precursor protein (APP) have now been shown to cause Alzheimer's disease in some families. Other genetic loci are now being discovered which relate to Alzheimer's disease in some families. Understanding the normal structure and function of the APP gene product will eventually provide avenues for developing specific therapeutic strategies targeted at the amyloid deposition in the Alzheimer's disease brain. Drugs which can inhibit or dissolve the amyloid, affect the synthesis and proteolysis of APP, or which regulate the activity of the APP gene all hold the promise of eventually yielding an effective treatment for Alzheimer's disease.
Structure Aggregation And Inhibition Of Alzheimer S Beta Amyloid Peptide A Beta
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Author : Qiuming Wang
language : en
Publisher:
Release Date : 2013
Structure Aggregation And Inhibition Of Alzheimer S Beta Amyloid Peptide A Beta written by Qiuming Wang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with Alzheimer's disease categories.
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.
Multiscale Molecular Simulations Of Cross Sequence Interactions Between Amyloid Peptides
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Author : Mingzhen Zhang
language : en
Publisher:
Release Date : 2017
Multiscale Molecular Simulations Of Cross Sequence Interactions Between Amyloid Peptides written by Mingzhen Zhang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with Aggregation (Chemistry) categories.
Amyloid aggregation have been implicated in the pathology of many neurodegenerative diseases, including prion disease, Alzheimer's disease (AD), type II diabetes (T2D), and Parkinson disease. Amyloid peptides undergo the nucleation-polymerization aggregation process, during which amyloid peptides experience structural conversions from unstructured monomers to critical nucleus, and eventually to amyloid fibrils containing dominant ß-sheet structures. Such common misfolding and aggregation characteristics, in some cases, drive cross-seeding interactions between amyloid peptides, which play a major role in the progression and transmission between the neurodegenerative diseases. In the experiments, the cross-seeding interactions between amyloid peptides including ß-amyloid (Aß)-islet amyloid peptides (IAPP), Aß-tau, Aß-prion, human IAPP-rat IAPP, and tau-synuclein amyloids have been extensively implicated. However, high-resolution evidence is still unavailable and little is known about how these two peptides interact with each other. In our research, we perform the multiscale molecular simulations to sysmetically study the cross-seeding interactions between different amyloid peptides at the atomic resolution, with the particular focus on the prediction of the atomic structures, the dynamic behavious in bulk and membrane enviroment, and the interface properties of the hIAPP-rIAPP and Aß-hIAPP cross-seeding assemblies. In Chapter I and II, we model and simulate different heteroassemblies formed by the amyloidogenic hIAPP and the nonamyloidogenic rIAPP peptides. The U-shaped hIAPP monomers and oligomers can interact with conformationally similar rIAPP to form stable complexes and to co-assemble into heterogeneous structures via the interfacial hydrogen bonds and hydrophobic contacts at ß-sheet regions. This work demonstrates the existence of cross-interactions between the two different IAPP peptides at the atomic level, providing an improved fundamental understanding of the cross-seeding of different amyloid sequences towards amyloid aggregation and toxicity mechanisms. In Chapter III, IV and V, we investigate the cross-seeding interactions between Aß and hIAPP using a combination of coarse-grained (CG) replica-exchange molecular dynamics (REMD), all-atom molecular dynamics (MD) simulations and Markov Chain Monte Carlo (MCMC) simulations. We for the first time obtain the full free energy landscape for Aß-hIAPP cross-seeding interactions, by which the atomic structure of Aß-hIAPP cross-seeding assembly is determined. Computational mutagenesis studies reveal that disruption of interfacial salt bridges largely disfavor the ß-sheet-to-ß-sheet association, highlighting the importance of salt bridges in the formation of cross-seeding assemblies. We also probe the behaviors of Aß-hIAPP cross-seeding assemblies on zwitterionic POPC and anionic POPC/POPG membranes, determining the specific orientations and demonstrating that electrostatic interactions are the major forces governing peptide-lipid interactions. This work confirms the cross-seeding interactions between Aß and hIAPP, explaining the potential pathological link between AD and T2D. The atomic insights into the cross-seeding intearctions between amyloid peptides obtained from this work are expected to improve the understanding of the amyloid peptides and inspire the peptide inhibitor design towards the neurodegenerative diseases.
Apolipoprotein E And Alzheimer S Disease
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Author : A.D. Roses
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Apolipoprotein E And Alzheimer S Disease written by A.D. Roses and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
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.
Tau Oligomers
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Author : Jesus Avila
language : en
Publisher: Frontiers E-books
Release Date : 2014-08-18
Tau Oligomers written by Jesus Avila and has been published by Frontiers E-books this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-08-18 with Medicine (General) categories.
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”.
Dementia With Lewy Bodies
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Author : John O'Brien
language : en
Publisher: CRC Press
Release Date : 2005-11-29
Dementia With Lewy Bodies written by John O'Brien and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005-11-29 with Medical categories.
Filling a noticeable gap in the market for a new text solely focused on Dementia with Lewy Bodies, this book discusses cutting-edge topics covering the condition from diagnosis to management, as well as what is known about the neurobiological changes involved. With huge progress having been made over the last decade in terms of the disorder
Methods Of Behavior Analysis In Neuroscience
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Author : Jerry J. Buccafusco
language : en
Publisher: CRC Press
Release Date : 2000-08-29
Methods Of Behavior Analysis In Neuroscience written by Jerry J. Buccafusco and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000-08-29 with Medical categories.
Using the most well-studied behavioral analyses of animal subjects to promote a better understanding of the effects of disease and the effects of new therapeutic treatments on human cognition, Methods of Behavior Analysis in Neuroscience provides a reference manual for molecular and cellular research scientists in both academia and the pharmaceutic
Amyloid Proteins
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Author : Einar M. Sigurdsson
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-02-02
Amyloid Proteins written by Einar M. Sigurdsson and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-02-02 with Science categories.
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.