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2007 Grant - Sanders
Modulation of Beta-Amyloid Production by CD147
Charles R. Sanders, Ph.D.
Vanderbilt University Medical Center
2007 Investigator-Initiated Research Grant
A complex of proteins called gamma-secretase helps to clip the beta-amyloid protein fragment, a key suspect in Alzheimer pathology, from a larger protein called amyloid precursor protein (APP). Previous research has found that the naturally occurring human protein CD147 is able to suppress beta-amyloid production by preventing the clipping of APP by gamma-secretase.
Charles R. Sanders, Ph.D., and colleagues hope to determine the mechanisms by which CD147 suppresses the harmful actions of gamma-secretase. The team will test two hypotheses. First, they will determine whether CD147 binds directly to APP and thus makes the protein less available for cleavage. If this theory proves incorrect, they will see whether CD147 binds instead to gamma-secretase and hinders the protein complex's ability to clip APP.
Dr. Sanders and colleagues will use an imaging technique called nuclear magnetic resonance (NMR) spectroscopy. The technique should enable them to identify the part of CD147 that may interact with APP or with gamma-secretase, and it should help them analyze the structure of the molecules created by such binding. Results of Dr. Sanders' study could lead to therapies for Alzheimer's disease that enhance the body's production of CD147.