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2007 Grant - Cistola
Structural Studies of the APP Transmembrane Domain
David Paul Cistola, M.D., Ph.D.
East Carolina University
Greenville, North Carolina
2007 Investigator-Initiated Research Grant
A key feature of Alzheimer's disease is the accumulation of beta-amyloid, a tiny protein fragment that is clipped from its parent molecule, amyloid precursor protein (APP). APP typically is embedded in the outer fatty membrane of healthy nerve cells. Previous research indicates that abnormalities in the structure of APP lead to the production of harmful beta-amyloid. However, scientists have not been able to identify these structural abnormalities precisely.
For their proposed grant, David Paul Cistola, M.D., Ph.D., and colleagues will use a newly developed method to analyze APP structures. This method involves an imaging technique called nuclear magnetic resonance (NMR) spectroscopy. It also employs nanodiscs, or specially engineered "copies" of brain cell membranes that enable researchers to study APP and other membrane-embedded proteins more easily in the laboratory. Using this technique, Dr. Cistola's team will examine the three-dimensional structures of different APP variations. They hope to identify factors that may alter these structures, thus affecting the production of beta-amyloid. Such factors may include mutations in APP itself or alterations in the cholesterol content of the cell membrane.
Results of Dr. Cistola's study could lead to new therapeutic strategies for preventing the accumulation of beta-amyloid in Alzheimer's disease.