Download or read book Mathematical Models of Amyloid beta Production Aggregation and Treatment in Alzheimer s Disease written by Joseph H. Rosenthal and published by . This book was released on 2015 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Time Scale Analysis of a Mathematical Model for Alzheimer s Disease Based on the Metal Hypothesis written by Eda Asili and published by . This book was released on 2017 with total page 119 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aggregation of amyloid-beta by self-assembly into oligomers or amyloids is a central event in Alzheimer’s disease. In this dissertation, I propose a mathematical model as a set of coupled kinetic equations that governs the self-assembly of amyloid-beta filaments in the presence of transition-metal ions. Metal ions have been hypothesized as an important factor in the pathogenesis of AD. There is a considerable literature supporting the impact of metal ions such as copper (Cu), zinc (Zn) and iron (Fe) in many critical aspects of AD and other neurodegenerative diseases. Our study includes Cu and Zn as main transition-metal ions, where their coordination to amyloid-beta regulates the aggregation process in vivo. Metal ions mostly affect the nucleation phase and change both the structure and the charge of amyloid-beta. Our model describes the general features of the kinetics of fragmenting filamentous structures. The numerical simulations reveal a four timescale dynamics related to three important events, which are the formation of the amyloid-metal, the homogeneous aggregation of the filaments and the non-homogeneous aggregation of the protein-metal. The method of singular perturbation is used to discern between these timescales. These results are studied in the framework of slow-fast systems. We also compare the metal with the non-metal dynamics and apply optimization theory for realistic values of reaction rates. Simulations shows that in certain cases the presence of metal accelerates the aggregation of filaments in a drastic way.
Download or read book Computational Modeling of Drugs Against Alzheimer s Disease written by Kunal Roy and published by Springer Nature. This book was released on 2023-06-30 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition volume expands on the previous edition with updated descriptions on different computational methods encompassing ligand-based, structure-based, and combined approaches with their recent applications in anti-Alzheimer drug design. Different background topics like recent advancements in research on the development of novel therapies and their implications in the treatment of Alzheimer’s Disease (AD) have also been covered for completeness. Special topics like basic information science methods for insight into neurodegenerative pathogenesis, drug repositioning and network pharmacology, and online tools to predict ADMET behavior with reference to anti-Alzheimer drug development have also been included. In the Neuromethods series style, chapter include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and thorough, Computational Modeling of Drugs Against Alzheimer’s Disease, Second Edition is a valuable resource for all researchers and scientists interested in learning more about this important and developing field.
Download or read book Tau Biology written by Akihiko Takashima and published by Springer Nature. This book was released on 2020-02-24 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book A Mathematical Model of the Impact of Novel Treatments on the A 03B2 Burden in the Alzheimer s Brain CSF and Plasma written by Lawrence M. Wein and published by . This book was released on 2001 with total page 60 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the advent of novel therapies for AD, there is a pressing need for biomarkers that are easy to monitor, such as the amyloid-beta levels in the cerebrospinal fluid (CSF) and plasma. To gain a better understanding of the explanatory power of these biomarkers, we formulate and analyze a compartmental mathematical model for the amyloid-beta accumulation in the brain, CSF and plasma throughout the course of Alzheimer's treatment. Our analysis reveals that the total amyloid-beta burden in the brain is dictated by a unitless quantity called the polymerization ratio, which is the product of the production and elongation rates divided by the product of the fragmentation and loss rates. In this ratio, the production rate and loss rate include a source and sink term, respectively, related to the intercompaxtmental transport. Our results suggest that production inhibitors are likely to reduce the amyloid-beta levels in all three compartments. In contrast, agents that ingest monomers off of polymers, or that increase fragmentation or block elongation, may also reduce amyloid-beta burden in the brain, but may produce little change in or even transiently increase CSF and plasma amyloid-beta levels. Hence, great care must be taken when interpreting these biomarkers. Keywords: amyloid beta, mathematical model.
Download or read book A Mathematical Model of the Impact of Novel Treatments on the A beta Burden in the Alzheimer s Brain CSF and Plasma written by Lawrence M. Wein and published by . This book was released on 2001 with total page 60 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the advent of novel therapies for AD, there is a pressing need for biomarkers that are easy to monitor, such as the amyloid-beta levels in the cerebrospinal fluid (CSF) and plasma. To gain a better understanding of the explanatory power of these biomarkers, we formulate and analyze a compaxtmental mathematical model for the amyloid-beta accumulation in the brain, CSF and plasma throughout the course of Alzheimer's treatment. Our analysis reveals that the total amyloid-beta burden in the brain is dictated by a unitless quantity called the polymerization ratio, which is the product of the production and elongation rates divided by the product of the fragmentation and loss rates. In this ratio, the production rate and loss rate include a source and sink term, respectively, related to the intercompaxtmental transport. Our results suggest that production inhibitors are likely to reduce the amyloid-beta levels in all three compartments. In contrast, agents that ingest monomers off of polymers, or that increase fragmentation or block elongation, may also reduce amyloid-beta burden in the brain, but may produce little change in or even transiently increase CSF and plasma amyloid-beta levels. Hence, great care must be taken when interpreting these biomarkers. Keywords: amyloid beta, mathematical model.
Download or read book A Mathematical Model of the Impact of Novel Treatments on the Ab Burden in the Alzheimer s Brain Csf and Plasma written by Lawrence M. Wein and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the advent of novel therapies for AD, there is a pressing need for biomarkers that are easy to monitor, such as the amyloid-beta levels in the cerebrospinal fluid (CSF) and plasma. To gain a better understanding of the explanatory power of these biomarkers, we formulate and analyze a compaxtmental mathematical model for the amyloid-beta accumulation in the brain, CSF and plasma throughout the course of Alzheimer's treatment. Our analysis reveals that the total amyloid-beta burden in the brain is dictated by a unitless quantity called the polymerization ratio, which is the product of the production and elongation rates divided by the product of the fragmentation and loss rates. In this ratio, the production rate and loss rate include a source and sink term, respectively, related to the intercompaxtmental transport. Our results suggest that production inhibitors are likely to reduce the amyloid-beta levels in all three compartments. In contrast, agents that ingest monomers off of polymers, or that increase fragmentation or block elongation, may also reduce amyloid-beta burden in the brain, but may produce little change in or even transiently increase CSF and plasma amyloid-beta levels. Hence, great care must be taken when interpreting these biomarkers.
Download or read book Bioengineered Models of Alzheimer s Disease written by Laura Walker Simpson and published by . This book was released on 2019 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mathematical Models for Alzheimer s Disease written by Felix Winter and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mathematical Models for Alzheimer s Disease written by Felix Winter and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Impact of Novel Treatments on A beta Burden in Alzheimer s Disease written by David Lee Craft and published by . This book was released on 2001 with total page 62 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mutational Analysis of the Aggregation and Toxicity of the Amyloid Beta Peptide in a Drosophila Model of Alzheimer s Disease written by Leila Mohamed Luheshi and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Mathematical Models for Brain Diseases written by Verónica Tora and published by . This book was released on 2019 with total page 118 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer’s disease (AD) is characterized by the presence of two specific structures in brain of patients: senile plaques (SP) and neurofibrillary tangles (NTFs). Oligomers of beta amyloid protein are the main component of SP, while NFTs are constituted by oligomers of aberrantly phosphorylated tau protein. The aim of this thesis is to present two studies concerning the process of diffusion and agglomeration of tau protein first into fibrils and eventually up to neurofibrillary tangles. The aforesaid researches share the use of Smoluchowski-type equations (including diffusion and monomers production) on a finite weighted graph, which is conceived as a theoretical approximation of the human brain, where each vertex represents a cerebral area of interest, while the connections between them are described by the edges...
Download or read book Computational Modeling of Anti aggregation Effect of Non steroidal Anti inflammatory Drugs in Alzheimer s Amyloidogenesis written by Wenling Eileen Chang and published by . This book was released on 2011 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease (AD) represents a growing biomedical, social, and economical problem. Millions of people have suffered from the disease globally. Studies have shown that aggregated forms of amyloid [beta] peptide adversely affect neuronal function and may represent the causative agent in AD. It has been demonstrated that chronic treatment with ibuprofen and naproxen reduces the risk of AD and improves the behavioral impairment for patients with AD. This dissertation utilizes high performance parallel computing, all-atom molecular dynamics simulation, and protein-ligand docking to understand the mechanism of the anti-aggregation effect of ibuprofen and naproxen in Alzheimer's amyloidogenesis. The results reveal different mechanisms of ligand binding to the monomers and fibrils formed by A[beta] peptides implicated in AD. Binding to A[beta] monomers is mostly governed by ligand-amino acid interactions, whereas binding to the fibril is determined by the fibril surface geometry and interligand interactions. The antiaggregation effect of ibuprofen and naproxen is explained by direct competition between these ligands and incoming A[beta] peptides for binding to the fibril.
Download or read book Data driven Modeling of Neurodegeneration in Alzheimer s Disease written by Amelie Schäefer and published by . This book was released on 2022 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease constitutes one of the biggest public health challenges of our time. About one out of nine Americans over the age of 65 is affected today, with numbers rising steeply as our demographics shift towards an older society. The hallmarks of Alzheimer's disease entail an abnormal aggregation of the proteins amyloid-beta and tau in the brain, widespread brain atrophy, and gradually advancing cognitive impairment. The development of disease-modifying treatments requires early diagnosis and a deep understanding of disease causes and progression. However, to date much of our understanding of the early disease mechanisms and their interactions is vague and based on qualitative observations. In this thesis, we introduce computational models describing the prion-like aggregation of protein, the accumulation of pathological tau protein in the brain, and the coupling between tau pathology and regional tissue atrophy in Alzheimer's disease. Validating these models with longitudinal imaging data of real subjects allows us to identify numerical ranges for disease parameters on a personalized basis, thereby shifting our understanding of pathological events and causal relationships to a quantitative level. We leverage hierarchical modeling and Bayesian inference to take advantage of group level similarities and quantify uncertainty in our simulations. With the calibrated models we are able to generate personalized predictions forecasting how tau pathology and atrophy may evolve in a certain patient over time. Our approach also enables us to discover supporting evidence that the presence of amyloid-beta is a driver for tau pathology and tau-induced atrophy.
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”.
