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Developing an Alzheimer’s Disease Therapeutic: Identification and Validation of Signaling Pathways Involved in Small Molecule Induction of Nerve Growth Factor

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dc.contributor.advisor Couch, Robin D
dc.contributor.author Davis, Justin Bradford
dc.creator Davis, Justin Bradford
dc.date.accessioned 2016-09-28T10:23:06Z
dc.date.available 2016-09-28T10:23:06Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/1920/10460
dc.description.abstract Nerve growth factor (NGF) has been identified as a key protein involved in preventing neuronal cell death, a hallmark of neurodegeneration due to age and Alzheimer’s Disease. Recent preclinical and clinical Alzheimer’s Disease studies have noted a reduction in the rate of cognitive decline upon treatment with NGF. However, because NGF is unable to penetrate the blood-brain barrier, current means of delivering NGF to the brain are highly invasive and cost-prohibitive. An orally administered small molecule, capable of stimulating the upregulation of NGF in the brain, is preferred. Several small molecules that cause the upregulation of NGF have been discovered through serendipity, but their mechanisms of action are still poorly understood. A thorough investigation into the mechanisms of known inducers of NGF identified Protein Kinase C and the Mitogen Activated Protein Kinase pathway as critical to the upregulation of NGF protein. A series of protein specific agonists and antagonists was employed to validate select members of this signaling pathway, revealing promising targets for the development of neuroprotective therapeutics.
dc.format.extent 166 pages
dc.language.iso en
dc.rights Copyright 2016 Justin Bradford Davis
dc.subject Biochemistry en_US
dc.subject Microbiology en_US
dc.subject Chemistry en_US
dc.subject MAPK pathway en_US
dc.subject Nerve growth factor en_US
dc.subject phorbol 12-myristate 13-acetate en_US
dc.subject protein kinase c en_US
dc.title Developing an Alzheimer’s Disease Therapeutic: Identification and Validation of Signaling Pathways Involved in Small Molecule Induction of Nerve Growth Factor
dc.type Dissertation
thesis.degree.level Ph.D.
thesis.degree.discipline Chemistry and Biochemistry
thesis.degree.grantor George Mason University


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