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β-site Amyloid Precursor Protein-cleaving enzyme-1 (BACE1) is the key protein that facilitates the production of amyloid-β protein (Aβ), which is the major cause of the symptoms of Alzheimer’s Disease. It has been shown that Golgi-localized γ-ear-containing ADP-ribosylation factor binding protein 3 (GGA3) inversely regulates the level of BACE1 in in vitro model. In this experiment, 3 different ... read moretransgenic mouse lines overexpressing GGA3 (Wild type - WT, L276A, Quadruple Mutation D313A, D328A, D333A, D328A - QM) were analyzed to test the hypothesis that overexpression of GGA3 regulates BACE1 level in an in vivo model. Western Immunoblotting data analyzing hemi-brain homogenate samples showed that transgenic mouse lines WT, L276A and QM did not show significant suppression of endogenous BACE1 level compared to the non-transgenic control group as expected. An alternative hypothesis was made that GGA3 only regulates BACE1 over a certain range of expression level – once the target BACE1 level was reached, the suppression of GGA3 on BACE1 stops. The new hypothesis will be tested in future experiments. Submitted in partial fulfillment of the grant requirement of the Tufts Summer Scholars Program.read less
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