2008 Grants - Vetrivel

Exploring Beta-Secretase Activity in Lipid Raft Microdomains

Kulandaivelu S. Vetrivel, Ph.D.
University of Chicago
Chicago, Illinois

2008 New Investigator Research Grant

Beta-amyloid is a key suspect in Alzheimer pathology. Beta-secretase is one of the enzymes necessary for the production of beta-amyloid from its parent protein, amyloid precursor protein (APP). Increasing evidence indicates that beta-secretase and other enzymes necessary for the production of beta-amyloid reside in specialized regions within the cell called lipid raft microdomains. This finding is important because it may affect the development of drugs intended to block beta-amyloid production.

Kulandaivelu S. Vetrivel, Ph.D., and colleagues are studying how the beta-secretase enzyme is transported and localized to lipid raft microdomains. Such localization is known to be dependent on the attachment of specific fatty acid groups (S-palmitate) to the enzyme. To study this process further, Dr. Vetrivel and colleagues have developed genetically altered mice with mutant beta-secretase lacking sites where S-palmitate can attach to the enzyme.

Dr. Vetrivel and colleagues plan to use their mice to study the processing of APP into beta-amyloid, with the expectation that the mutant mice will produce less beta-amyloid. They also plan to study the process by which beta-secretase and related enzymes are transported to lipid raft microdomains. These studies may provide important insights into the cellular mechanisms responsible for the generation of beta-amyloid and may help identify strategies to prevent this key step in the Alzheimer's disease process.