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dc.contributor.advisorSun, Grace Y.eng
dc.contributor.authorShelat, Phullara B., 1978-eng
dc.date.issued2008eng
dc.date.submitted2008 Springeng
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.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on April 29, 2010).eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionVita.eng
dc.descriptionThesis advisor: Grace Y. Sun.eng
dc.description"May 2008"eng
dc.descriptionPh. D. University of Missouri-Columbia 2008.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Biochemistry.eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Alzheimer's disease (AD) is a neurodegenerative disorder affecting more than 20 million people worldwide. An increase in production of amyloid beta peptides (A[Beta]) and their aggregation to the oligomeric form is thought to contribute to neurotoxicity in the AD brain. cPLA2 is an enzyme responsible for hydrolysis of fatty acids in the sn-2 position of membrane phospholipids. Substantial attention has been paid to arachidonic acid (AA) because this lipid mediator is not only used for prostanoid synthesis but is also regarded as a retrograde transmitter. cPLA2 has been implicated in the pathogenesis of a number of neurodegenerative diseases including AD. Recent studies provided evidence for the production of reactive oxygen species (ROS) in association with glutamate excitotoxicity and involvement of NMDA receptors in A[Beta]-induced neurotoxicity. This study is focused on elucidating the role of NADPH oxidase, a superoxide producing enzyme, on the signaling pathway leading to cPLA2 activation and AA release in cortical neurons. Results show that A[Beta] and NMDA can produce ROS in neurons via NADPH oxidase and that this pool of ROS is important for ERK1/2 phosphorylation, cPLA2 phosphorylation and subsequent AA release. The study presented here identifies for the first time the importance of the ROS producing enzyme NADPH oxidase in the signaling pathway leading to A[Beta]-induced and NMDA receptor-mediated cPLA2 activation in neurons. This novel mechanism may contribute to a better understanding of the oxidative mechanism underlying the pathogenesis of AD.eng
dc.format.extentxii, 158 pageseng
dc.identifier.oclc610240226eng
dc.identifier.urihttps://hdl.handle.net/10355/7205
dc.identifier.urihttps://doi.org/10.32469/10355/7205eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campus of the University of Missouri--Columbia.eng
dc.source.originalSubmitted by University of Missouri--Columbia Graduate School.eng
dc.subject.lcshAlzheimer's disease -- Pathophysiologyeng
dc.subject.lcshAmyloid beta-protein -- Toxicologyeng
dc.subject.lcshAmyloid beta-protein -- Effect of drugs oneng
dc.subject.lcshNAD (Coenzyme)eng
dc.subject.lcshActive oxygeneng
dc.subject.lcshPhospholipase A2 -- Effect of drugs oneng
dc.subject.meshAlzheimer disease -- physiopathologyeng
dc.subject.meshAmyloid beta-protein -- Toxicityeng
dc.subject.meshNADPH Oxidase -- metabolismeng
dc.subject.meshReactive Oxygen Species -- metabolismeng
dc.subject.meshAmyloid beta-Protein -- pharmacologyeng
dc.subject.meshNADPH Oxidase -- drug effectseng
dc.subject.meshPhospholipases A2, Cytosolic -- metabolismeng
dc.subject.meshPhospholipases A2, Cytosolic -- drug effectseng
dc.subject.meshExtracellular Signal-Related MAP Kinases -- metabolismeng
dc.subject.meshExtracellular Signal-Related MAP Kinases -- drug effectseng
dc.subject.meshAnachidonic Acid -- metabolismeng
dc.titleAmyloid beta induces cPLA2 activation by an NADPH oxidase-dependent mechanism in neuronseng
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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