Generation of DNA Constructs and Cell Lines Over-Expressing the Subunits of the Gamma Secretase Complex in Alzheimer's Disease

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.

Rights

This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

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