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dc.contributor.advisorSun, Grace Y.eng
dc.contributor.authorHe, Yan, 1979-eng
dc.date.issued2011eng
dc.date.submitted2011 Springeng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on October 24, 2012).eng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionDissertation advisor: Dr. Grace Y. Suneng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionVita.eng
dc.descriptionPh. D. University of Missouri-Columbia 2011.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Biochemistry.eng
dc.description"May 2011"eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Alzheimer's disease (AD) is characterized by a progressive decline in memory and cognitive function together with increased oxidative stress in the brain. Although there is increasing evidence indicating the involvement of oligomeric amyloid-beta peptides (Aβ) in mediating oxidative damage to neurons, the mechanism(s) about how these peptides alter neuronal functions remains elusive. Recent studies from our laboratory have demonstrated the effects of N-methyl-D-aspartic acid (NMDA) and oligomeric Aβ to produce reactive oxygen species (ROS) from NADPH oxidase, and stimulate downstream signaling pathways leading to activation of mitogen-activated protein kinases (MAPKs) and cytosolic phospholipase A2 (cPLA2) in neurons. In this study, we investigated the effects of prolonged exposure of neurons to oligomeric Aβ and their response to NMDA-induced Ca2+ influx, release of arachidonic acid (AA), mitochondrial dysfunction, and ROS production. Results demonstrated that prolonged exposure of neurons to Aβ caused mitochondrial dysfunction, a decrease in NMDA-induced Ca2+ influx and AA release, and an increase in levels of ROS. Neuronal impairments induced by Aβ could be blocked by gp91ds-tat, a specific inhibitor for NADPH oxidase as well as other ROS scavengers, including the botanical phenolic compound, epigallochatechin-gallate (EGCG) from green tea. These studies thus identified the involvement of NADPH oxidase as a source of ROS in the cytotoxic effects of Aβ. These results also provide a neuron model for identifying novel botanical antioxidants to protect against neurotoxic effects of Aβ oligomers.eng
dc.format.extentxiv, 171 pageseng
dc.identifier.merlinb93927885eng
dc.identifier.oclc817217238eng
dc.identifier.urihttps://hdl.handle.net/10355/15839
dc.identifier.urihttps://doi.org/10.32469/10355/15839eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campuses of the University of Missouri.eng
dc.source.originalSubmitted by University of Missouri--Columbia Graduate School.eng
dc.subjectNMDA receptoreng
dc.subjectoligomeric amyloid-beta peptideseng
dc.subjectoxidative damageeng
dc.subjectmitochondrial dysfunctioneng
dc.subjectbotanical antioxidantseng
dc.subject.meshAmyloid beta-peptides -- pharmacologyeng
dc.subject.meshCatechin -- analogs & derivativeseng
dc.subject.meshCatechin -- pharmacologyeng
dc.subject.meshN-Methylaspartate -- pharmacology|Reactive Oxygen Species -- metabolismeng
dc.subject.meshNADPH Oxidase -- metabolismeng
dc.subject.meshArachidonic Acid -- metabolismeng
dc.subject.meshNeurons -- drug effectseng
dc.subject.meshNeuroprotective Agents -- pharmacologyeng
dc.titleAmyloid-beta toxicity in neurons and potential botanical compounds for prevention of Alzheimer's diseaseeng
dc.typeThesiseng
thesis.degree.disciplineBiochemistry (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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