Current Search: Amyloid beta-Peptides (x)
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- Title
- Role of the N-Terminal Hydrophilic Region of Amyloid Beta Peptide in Amyloidogenesis, Membrane Interaction and Toxicity Associated with Alzheimer’s Disease.
- Creator
- Morris, Clifford M., Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Alzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain...
Show moreAlzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain understanding on the electrostatic and hydrophobic constituents of the mechanism. This was achieved by substituting specific charged residues located in the NTR of Aβ40 and investigating their effects through a variety of techniques. We also investigated the role of NTR charged residues in their interaction with supported phospholipid bilayer membranes through the use of Quartz Crystal Microbalance with Dissipation (QCM-D) monitoring to gain insight on the mechanistic details of the interaction. To further understand the implications of substituting charged NTR residues on membrane interaction, pore formation and damage, we utilized a carboxyfluorescein dye leakage assay to quantify the membrane damage caused by Aβ40 and the NTR mutants. We also performed neurotoxicity assay with SH-SY5Y neuroblastoma cells to shed light on the effects of NTR substitutions on cellular toxicity. Finally, we synthesized a polymer, trimethyl chitosan (TMC), and utilized it as a polyelectrolyte monitor of electrostatic interactions occurring between TMC and the NTR of Aβ40. Our results demonstrate that the NTR charged residues of Aβ40 contribute significantly to the aggregation process, amyloidogenesis, and phospholipid membrane interaction and perturbation by means of electrostatic, thermodynamic and hydrophobic forces.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013246
- Subject Headings
- Alzheimer's disease, Amyloid beta-Peptides, Amyloid
- Format
- Document (PDF)
- Title
- Studying the Effects of Lipid Membranes and Polysaccharides on the Amyloidogenicity of Fragments of Amyloid Beta.
- Creator
- Petersen, Katherine, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
The amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely...
Show moreThe amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely resulting in the etiology of AD. In this study, two fragments are used, the 23-residue N-terminal fragment, Aβ23 and the 30-residue C-terminal fragment, Aβ11-40, to better understand the role of the N and C-terminus in the aggregation of Aβ peptide. Aβ11-40 has also been found in the brains of AD patients, playing a biological role in the disease. This study used analytical and biophysical techniques to systematically synthesize, purify, characterize, and study these fragments' aggregation in different conditions. We investigated the effects of lipid membranes on the aggregation of Aβ23 and Aβ11-40 and the activities of these peptides in inducing membrane damage. The results show that the aggregation of Aβ23 was increased in the presence of lipid membranes, likely due to favorable electrostatic interactions. However, the aggregation of Aβ11-40 was not influenced by lipid membranes. A dye leakage study was carried out to study the membrane damage occurring as a result of fragments' interaction with lipid membranes. The results showed that neither fragment had a profound effect on membrane destruction, although the charge of the lipid head seemed to play a role. This work's second study focused on the effect of three specific polysaccharides, heparin, chitosan (CHT), and trimethyl chitosan (TMC), on the aggregation of Aβ23 and Aβ11-40. The results showed that for Aβ23, heparin increased aggregation, while both CHT and TMC decreased aggregation. However, for Aβ11-40, both heparin and CHT did not affect aggregation, while TMC decreased aggregation.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014294
- Subject Headings
- Amyloid beta-Peptides, Alzheimer's disease
- Format
- Document (PDF)
- Title
- Effect of amyloid beta on nutrient uptake and ATP in the brain cells.
- Creator
- To, William, Tao, Rui, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Unintentional weight loss in older adults often precedes Alzheimer’s disease (AD). Positron emission tomography (PET) scan reveals that AD patients exhibit reduced uptake of fluorodeoxyglucose into brain cells, defined as ‘hypometabolism’. However, cellular mechanisms underlying weight loss and hypometabolism have not received much attention. The primary goal of the study was to test the hypothesis that cells become starved in confrontation with amyloid beta proteins (Aβ), which are...
Show moreUnintentional weight loss in older adults often precedes Alzheimer’s disease (AD). Positron emission tomography (PET) scan reveals that AD patients exhibit reduced uptake of fluorodeoxyglucose into brain cells, defined as ‘hypometabolism’. However, cellular mechanisms underlying weight loss and hypometabolism have not received much attention. The primary goal of the study was to test the hypothesis that cells become starved in confrontation with amyloid beta proteins (Aβ), which are increasingly aggregated in the AD brain. Cellular ATP is known as a biomarker indicating for cell starvation. We found that Aβ caused a dose-dependent reduction in ATP of astrocytes. This effect was similar to those of cells being deprived from nutrients (i.e., glucose, pyruvate and glutamine). Together, the data of the present study support the hypothesis that cell starvation is likely associated with weight loss and hypometabolism in AD patients.
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FA00013941
- Subject Headings
- Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Adenosine Triphosphate
- Format
- Document (PDF)
- Title
- DISSECTING THE MECHANISTIC ROLES OF REGULATORS IN MEDIATING AMYLOID-BETA AMYLOIDOGENESIS.
- Creator
- Shen, Fengyun, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Alzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and...
Show moreAlzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and carnosine, phospholipids, and β-hairpins on Aβ aggregation to dissect their mechanistic roles in the amyloidogenesis of Aβ. We first systematically studied the kinetic impact of Zn2+ on the aggregation of Aβ40 and Aβ40-M. Our results show that the presence of Zn2+ transforms the Aβ40 aggregation kinetics from a single sigmoidal to a biphasic process, while the aggregation of Aβ40-M is significantly suppressed by Zn2+. We also found that a nature dipeptide, carnosine, remarkably decreases the activity of Zn2+ on modulating Aβ aggregation, although it has a weak direct effect on the peptide aggregation kinetics. Second, we investigated the activities of Aβ40 and Aβ42 in inducing membrane damage and the effects of lipid membranes on the aggregation of these peptides using liposome models containing mitochondrial-specific phospholipid–cardiolipin (CL).
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014314
- Subject Headings
- Alzheimer's disease, Amyloid beta-Peptides, Neurodegenerative Diseases
- Format
- Document (PDF)
- Title
- Amyloid Beta Clearance in Alzheimer’s Disease: A PET Imaging and Data Science Study.
- Creator
- Hall, Rudolf, Tao, Rui, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Amyloid beta (Aβ), a byproduct of amyloid precursor protein, is constantly cleared from the CNS. Aβ kinetics are visualized using 18F-florbetapir PET imaging, typically analyzed through 2D coregistration with MRI or CT followed by visual evaluation. Aβ was thought to coexist in the white matter of both Alzheimer’s disease (AD; Aβ+) patients and cognitively unimpaired (CU; Aβ-) individuals. However, this coexistence is likely a misperception of 2D imaging. In this study, data science...
Show moreAmyloid beta (Aβ), a byproduct of amyloid precursor protein, is constantly cleared from the CNS. Aβ kinetics are visualized using 18F-florbetapir PET imaging, typically analyzed through 2D coregistration with MRI or CT followed by visual evaluation. Aβ was thought to coexist in the white matter of both Alzheimer’s disease (AD; Aβ+) patients and cognitively unimpaired (CU; Aβ-) individuals. However, this coexistence is likely a misperception of 2D imaging. In this study, data science techniques were used to evaluate PET images, transforming Aβ imaging into topographical pixel arrays for 3D reconstruction. Canal-like networks in the brain, skull, and neck were discovered to be part of the non-CNS fluid (NCF) compartment, which quarantines Aβ. In CU/Aβ- subjects, Aβ is transported to peripheral lymphatics. In AD/Aβ+ subjects, Aβ becomes congested in the NCF, diffusing into CNS interstitial fluid, leading to progression and neurodegeneration.
Show less - Date Issued
- 2024
- PURL
- http://purl.flvc.org/fau/fd/FA00014531
- Subject Headings
- Alzheimer Disease, Amyloid beta-Peptides, Positron-Emission Tomography
- Format
- Document (PDF)