2012 Grants - Vertivel

Proteomic Analysis of Gamma-Secretase Residing in Raft Domains

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

2012 New Investigator Research Grant

Gamma-secretase is a key molecule in Alzheimer’s disease. It is one of two main protein complexes in the biochemical pathway that produces beta-amyloid, a protein fragment that can aggregate to form amyloid plaques in the brain. Because of this important role of gamma-secretase, scientists have worked to develop drugs to inhibit it. However, gamma-secretase has many other important functions, so inhibiting its function may have undesirable side effects.

In previous research, Kulandaivelu S. Vetrivel, Ph.D., and colleagues found that some copies of gamma-secretase inside cells are attached to small particles of fat-like molecules called lipid rafts. The researchers also found evidence that the production of beta-amyloid may occur at these lipid rafts, whereas other functions of gamma-secretase may be performed elsewhere.

Dr. Vetrivel and colleagues have proposed a series of studies to further characterize how gamma-secretase functions when attached to lipid rafts. They plan to use biochemical techniques to identify other proteins that work with gamma-secretase when it is in this specialized compartment. The researchers will then use gene manipulation to characterize how those proteins help gamma-secretase produce beta-amyloid. These studies will enhance our understanding of how beta-amyloid is produced, and they may help to identify new ways to inhibit gamma-secretase that have fewer side effects.