An in vivo model of Parkinson's disease induced by prostaglandin J2 and HSP105 as a potential therapeutic target.
Item
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Title
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An in vivo model of Parkinson's disease induced by prostaglandin J2 and HSP105 as a potential therapeutic target.
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Identifier
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AAI3310650
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identifier
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3310650
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Creator
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Pierre, Sha-Ron.
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Contributor
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Adviser: Maria Figueiredo-Pereira
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Date
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2008
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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Chronic neuroinflammation is implicated in Parkinson's disease (PD), a disorder that exhibits accumulation of ubiquitinated proteins in neuronal inclusions (Lewy bodies), indicating a malfunction of the normal process of protein turnover in the affected areas. J2 prostaglandins (PGJ2) are neurotoxic products of inflammation that were shown in cellular models to impair the ubiquitin/proteasome pathway (UPP) causing the accumulation of ubiquitinated proteins into aggregates. J2 prostaglandins are derived from PGD2, the major prostanoid in the mammalian brain. Using PGJ2 as a prototype for a neuroinflammation toxicant product, we established an in vivo model of Parkinson's disease that mimics neuroinflammation. We administered PGJ2 into the substantia nigra and striatum of adult male FVB mice by microinjection. PGJ2 injections induced concentration-dependent behavioral changes indicative of neuronal damage in the affected areas. Immunohistochemical analyses further supported and characterized the neuronal damage induced by the PGJ2 microinjections. This PD animal model involving PGJ2-induced toxicity is a valuable tool to address the pathogenic mechanisms that converge on the onset of PD neuroinflammation. In addition, we addressed the potential of increasing the levels of the molecular chaperone HSP105 to prevent the toxic effects of neuroinflammation. This approach could be tested as a protective strategy with our new PD model.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
