Award Date

1-1-2006

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Committee Member

Bryan L. Spangelo

Number of Pages

108

Abstract

A paucity of gamma-aminobutyric acid (GABA) levels is thought to encourage cytokine release in Alzheimer's disease (AD). A mechanistic investigation into the GABA-mediated suppression of the synergistic release of interleukin (IL)-6 by IL-1beta and tumor necrosis factor (TNF)-alpha is presented. Preliminary results indicate that p38 and nuclear factor (NF)-kappaB are essential for the synergistic release of IL-6 by IL-1beta and TNF-alpha. Both IL-1beta and TNF-alpha are able to stimulate the phosphorylation of p38, however, no synergistic stimulation was observed. IL-1beta or TNF-alpha is able to stimulate the degradation of the NF-kappaB inhibitor, IkappaB-alpha, with no change in IkappaB-beta. Interestingly, TNF-alpha is able to accelerate IkappaB-alpha degradation in the presence of IL-1beta. While GABA is unable to suppress IkappaB-alpha degradation and the phosphorylation of p38 by IL-1beta and TNF-alpha, it is postulated that GABA may be able to inhibit IL-6 concentrations by lessening the rate of IkappaB-alpha degradation.

Keywords

Acid; Aminobutyric; Astrocytic; Cytokine; Gamma; Induction; Inhibits; Interleukin; Mechanistic; Mediated; Release; Study; Synergistic

Controlled Subject

Biochemistry; Pharmacology; Neurosciences; Cellular biology

File Format

pdf

File Size

2140.16 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

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