Abstract

Alzheimer's disease (AD) is an age progressive neurodegenerative brain disorder, affecting 37 million people worldwide. Cleavage of amyloid precursor protein by ?- and ?-secretase produces the amyloid-beta (A?) protein, which significantly contributes to AD pathogenesis. The A? aggregates, formed at the surface of neurons and intracellularly, cause neurotoxicity and decrease synaptic function. Inhibiting or degrading A? accumulation is a key goal for development of new AD treatments. Evidence shows that human Myelin Basic Protein (MBP) binds to and degrades A? thereby, preventing cytotoxicity. A potential method for oral drug delivery that will allow plant-derived bioencapsulated MBP to pass through intestinal epithelium and bypass denaturing stomach acidity is quite novel. Cholera Toxin B subunit (CTB), when fused with MBP, can serve as a vehicle for oral delivery of this chloroplast expressed therapeutic protein into the systemic circulation. Within chloroplast, CTB forms a pentameric structure that binds to GM1 ganglioside receptors, allowing receptor-mediated endocytosis. In order to investigate protein entry through neuronal GM1 receptors, we first created CTB fused to the green fluorescent protein (GFP). Incubation of this fusion protein with human neuroblastoma cells resulted in GFP entry into these cells whereas GFP alone was unable to enter. Similarly, co-incubation of CTB-MBP, via neuronal GM1 binding, allowed MBP to reduce neurotoxicity of A?42 treated cells by 37.1%. Delivery of CTB-MBP through GM1 receptor mediated binding should therefore facilitate oral administration, storage, heat stability and low cost AD treatment.

Notes

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Thesis Completion

2012

Semester

Summer

Advisor

Daniell, Henry

Degree

Bachelor of Science (B.S.)

College

Burnett School of Biomedical Sciences

Degree Program

Molecular Biology and Microbiology

Subjects

Dissertations, Academic -- Medicine;Medicine -- Dissertations, Academic

Format

PDF

Identifier

CFH0004249

Language

English

Access Status

Open Access

Length of Campus-only Access

None

Document Type

Honors in the Major Thesis

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