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Design of antioxidant nanotherapeutics for attenuation of atherogenesis and neuroinflammation

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TitleInfo
Title
Design of antioxidant nanotherapeutics for attenuation of atherogenesis and neuroinflammation
Name (type = personal)
NamePart (type = family)
Chmielowski
NamePart (type = given)
Rebecca Ann
NamePart (type = date)
1979-
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Rebecca Ann Chmielowski
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
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Moghe
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Prabhas V
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Prabhas V Moghe
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Advisory Committee
Role
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chair
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Roth
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Charlie
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Charlie Roth
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Advisory Committee
Role
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internal member
Name (type = personal)
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Uhrich
NamePart (type = given)
Kathryn E
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Kathryn E Uhrich
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Baum
NamePart (type = given)
Jean
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Jean Baum
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Joseph
NamePart (type = given)
Laurie B
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Laurie B Joseph
Affiliation
Advisory Committee
Role
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outside member
Name (type = personal)
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Tugcu
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Nihal
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Nihal Tugcu
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Advisory Committee
Role
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outside member
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Rutgers University
Role
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degree grantor
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NamePart
School of Graduate Studies
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school
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Text
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theses
OriginInfo
DateCreated (qualifier = exact)
2018
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2018-01
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2018
Place
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xx
Language
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eng
Abstract (type = abstract)
Atherosclerosis and Parkinson’s disease are both characterized by the uncontrolled uptake of modified proteins in chronic inflammatory cells, macrophages/microglia. The initial stages of atherosclerosis are characterized by oxidation of low density lipoprotein and its uptake by macrophages, which can lead to plaque progression in the arterial wall and possibly heart attack or stroke. Formation and increase of misfolded aggregates of proteins such as alpha synuclein (α-synuclein) are a key factor in several neurodegenerative diseases including Parkinson’s disease. Both classes of diseases are exacerbated in macrophages/microglia due to a strong inflammatory component, which has been challenging to treat. The anti-atheroprotective and anti-inflammatory properties of antioxidants create an attractive target for treatment of atherosclerosis and Parkinson’s disease. We propose a library of antioxidant nanoparticles that have the potential to address critical needs for both atherosclerosis and Parkinson’s disease. For atherosclerosis applications, we advanced the delivery and formulation of antioxidants through the development of ferulic acid-based polymer nanoparticles, which are completely biodegradable and can achieve a sustained and tunable release of ferulic acid to limit macrophage foam cell formation. The ferulic acid-based polymer nanoparticles attenuated macrophage lipogenesis and reactive oxygen species generation. The cellular mechanism of the nanoparticle efficacy involved the down regulation of the expression of three scavenger receptors, which are critical for modulation of lipid uptake in macrophages. For neuroinflammatory applications, we developed a dual antioxidant nanoparticle consisting of ferulic acid and tannic acid, which significantly reduced the generation of -synuclein fibrils. This result suggests that the combination of antioxidants and the configuration of nanoparticle vehicles could be important factors for inhibiting -synuclein fibril formation. Overall, antioxidant nanotherapeutics may be promising technologies for inhibition of early stages of both atherosclerosis and Parkinson’s disease.
Subject (authority = RUETD)
Topic
Chemical and Biochemical Engineering
Subject (authority = ETD-LCSH)
Topic
Atherosclerosis--Treatment
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8666
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiv, 112 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Rebecca Ann Chmielowski
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T32N55GH
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Chmielowski
GivenName
Rebecca
MiddleName
Ann
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-01-11 22:04:11
AssociatedEntity
Name
Rebecca Chmielowski
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2018-01-13T00:59:12
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2018-01-13T00:59:12
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