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Effects of small molecule modulators and Phospholipid Liposomes on βeta-amyloid (1-40) Amyloidogenesis
Title
Effects of small molecule modulators and Phospholipid Liposomes on βeta-amyloid (1-40) Amyloidogenesis.
Creator
Morris, Clifford, Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Beta-Amyloid (1-40) (Aβ40) is an aggregation prone protein, which undergoes a nucleation-dependent aggregation process causing the pathological neurodegeneration by amyloid plaque formation implicated in Alzheimer’s disease. In this thesis, we investigated the effects of small molecule modulators extracted from the marine invertebrate Pseudopterogorgia elisabethae on the Aβ40 amyloidogenic process using in- vitro ThT fluorescence assay and atomic force microscopy. We also investigated the...
Show moreBeta-Amyloid (1-40) (Aβ40) is an aggregation prone protein, which undergoes a nucleation-dependent aggregation process causing the pathological neurodegeneration by amyloid plaque formation implicated in Alzheimer’s disease. In this thesis, we investigated the effects of small molecule modulators extracted from the marine invertebrate Pseudopterogorgia elisabethae on the Aβ40 amyloidogenic process using in- vitro ThT fluorescence assay and atomic force microscopy. We also investigated the effects of neutral and anionic phospholipid liposomes on Aβ40 aggregation. Our results show that a marine natural product Pseudopterosin-A and its derivatives can suppress and modulate the Aβ40 aggregation process. Furthermore, our results demonstrate that a neutral phospholipid liposome inhibits Aβ40 fibril formation, whereas the anionic liposomes promote it.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004453, http://purl.flvc.org/fau/fd/FA00004453
Subject Headings
Aggregation (Chemistry), Alzheimer's disease -- Pathogenesis, Alzheimer's disease -- Research, Amyloid beta protein, Molecular biology, Molecular dynamics, Prions, Proteins -- Metabolism -- Disorders
Format
Document (PDF)
Studies of Site-Specific Dynamics of Aβ Amyloid Formation and Effect of Macromolecules on Aβ Amyloidogenesis
Title
Studies of Site-Specific Dynamics of Aβ Amyloid Formation and Effect of Macromolecules on Aβ Amyloidogenesis.
Creator
Liu, Haiyang, Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
The aim of this dissertation was 1) to explore early stage aggregation kinetic behavior of Amyloid-β 1-40 (Aβ1-40) by incorporation of unnatural amino acid pcyanophenylalanine as a site-specific fluorescence reporter, 2) to explore the effect of macromolecules on the aggregation of Aβ1-40. Chapter One provides an introduction of Alzheimer’s disease as an amyloidogenic disease, amyloidogenic peptide and amyloid formation. Details were shown about the research progress of Aβ1-40 aggregation and...
Show moreThe aim of this dissertation was 1) to explore early stage aggregation kinetic behavior of Amyloid-β 1-40 (Aβ1-40) by incorporation of unnatural amino acid pcyanophenylalanine as a site-specific fluorescence reporter, 2) to explore the effect of macromolecules on the aggregation of Aβ1-40. Chapter One provides an introduction of Alzheimer’s disease as an amyloidogenic disease, amyloidogenic peptide and amyloid formation. Details were shown about the research progress of Aβ1-40 aggregation and Aβ1-40’s interaction with polyelectrolytes, and how treatments studies were designed. In Chapter two, using Aβ1-23 as a model molecule, the distinct site-specific dynamics was identified, during amyloid formation, and the structural characteristics of amyloid fibrils were defined by using an unnatural amino acid, p-cyanophenylalanine, as a sensitive fluorescent and Raman probe. The results reveal distinct local environmental changes of specific residues during the aggregation of Aβ1-23. The results also suggest that an edge-to-face aromatic interaction between the F4 and F19 residues from the adjacent in-register β-strands plays a key role in the conformational conversion to form and stabilize β-sheet structure. In Chapter Three, p-cyanophenylalanine was incorporated in the full sequence of Aβ1-40. Site-specific information from p-cyanophenylalanine fluorescence was studied and summarized. In Chapter Four, the inhibiting effect of an anionic polyelectrolyte poly(4- styrenesulfonate) (PSS) on the aggregation of Aβ1-40 peptide was reported. The results demonstrate the strong inhibition potential of PSS on the aggregation of Aβ1-40. Additional studies indicate that the presence of both aliphatic backbone as well as aromatic side chain group in PSS is essential for its inhibition activity. In Chapter Five, it was investigated the effect of two polyelectrolytes, chitosan (CHT) and N-trimethyl chitosan chloride (TMC), on the aggregation of Aβ1-40. Results show that both CHT and TMC exhibit a concentration-dependent decrease of amyloid aggregation suggesting their application as amyloid assembly inhibitors. Their binding mechanism was investigated by computational modeling which shows that Aβ1-40 monomer was primarily stabilized by electrostatic interactions with charged amine and quaternary amines of CHT and TMC respectively. Chapter Six, describes all experimental procedures and instrument setup in detail.
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FA00004769, http://purl.flvc.org/fau/fd/FA00004769
Subject Headings
Alzheimer's disease--Research., Alzheimer's disease--Pathogenesis., Molecular biology., Molecular dynamics., Prions., Amyloid beta-protein.
Format
Document (PDF)
Development and testing of a measure of Alzheimer’s disease knowledge in a rural Appalachian community
Title
Development and testing of a measure of Alzheimer’s disease knowledge in a rural Appalachian community.
Creator
Weise, Lisa K., Williams, Christine L., Christine E. Lynn College of Nursing
Abstract/Description
Rural West Virginia has a very high percentage of older adults. The age-related disease of Alzheimer’s threatens the health of older Appalachians, yet research on Alzheimer’s disease (AD) in this population is scarce. In order to improve screening rates for cognitive impairment, Appalachians need to understand their vulnerability. The first step would be to assess their knowledge about AD but a suitable AD knowledge test has not been developed. The purpose of this study was to test the...
Show moreRural West Virginia has a very high percentage of older adults. The age-related disease of Alzheimer’s threatens the health of older Appalachians, yet research on Alzheimer’s disease (AD) in this population is scarce. In order to improve screening rates for cognitive impairment, Appalachians need to understand their vulnerability. The first step would be to assess their knowledge about AD but a suitable AD knowledge test has not been developed. The purpose of this study was to test the reliability and validity of a new measure of knowledge about AD that is culturally congruent, and to examine factors that may predict AD knowledge in this rural population. A correlational descriptive study was conducted with 240 participants from four samples of older adults in south central rural Appalachian West Virginia using surveys and face-to-face interviews. Results from tests for stability, reliability including Rasch modeling, discrimination and point biserial indices, and concurrent, divergent, and construct validity were favorable. Findings were that although more diversity in test item difficulty is needed, the test discriminated well between persons with higher and lower levels of education [F(2, 226) = 170.51, p = .001]. Using multiple regression, the predictors of AD knowledge included caregiver status, miles from a healthcare provider, gender, and education; (R2=.05, F(4,187) = 2.65, p =. 04). Only years of education accounted for a significant proportion of unique variance in predicting the total BKAD score (t = 2.14, p =. 03). Implications include the need for further tool refinement, testing for health literacy, coordination with recent statewide efforts to educate the public regarding AD, and community based participatory research in designing culturally effective education programs that will ultimately increase screening and detection of Alzheimer’s disease in rural populations.
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Date Issued
2013
PURL
http://purl.flvc.org/fau/fd/FA0004074
Subject Headings
Alzheimer's disease -- Diagnosis -- Social aspects, Alzheimer's disease -- Research -- Methodology, Health literacy -- West Virginia -- Appalachian Region, Southern, West Virginia -- Appalachian Region, Southern -- Social aspects
Format
Document (PDF)