Date of Award

2010

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Gilchrist, Sandra

Keywords

Alzheimer's, Genetics, Gamma-Secretase

Area of Concentration

Biology

Abstract

Alzheimer�s disease is a neurodegenerative, irreversible disease whose cause is believed to be amyloid beta plaques and neurofibrillary tau tangles. Amyloid beta is a 40 or 42 amino acid peptide produced by cleavage of a larger protein, amyloid precursor protein (APP). Two enzymes called beta secretase and gamma secretase are responsible for the production of amyloid beta. A third enzyme, alpha secretase, may cleave before beta secretase and does so within the amyloid beta region and thus precludes its production. Much of the research aimed at finding a cure for Alzheimer�s disease focuses on reducing amyloid beta levels through blockage of beta secretase or gamma secretase. Unlike alpha and beta secretase, gamma secretase is a complex consisting of four subunits and eight isoforms of those subunits: Presenilins (PS1/PS2), Aph1 (APh1AL/APh1AS/APh1B), nicastrin, and Presenilin enhancer (PEN-2). Because of the subunits, gamma secretase is viewed as a target for inhibition or modulation. The work presented here isolated the genes for these subunits in order to generate constructs that were transfected into SH-SY5Y cells. Each subunit was inserted into a different mammalian expression vector so that in the future, different combinations of subunits can be made with the option of blocking the expression of certain subunits. As a whole, the cell lines will be used for drug testing as well as studying the interactions between subunits.

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