Ming Guo, M.D., Ph.D.
University of California
Los Angeles, California

2003 New Investigator Research Grant

A key suspect in Alzheimer pathology is a protein fragment called beta-amyloid. It is clipped from its parent molecule in two steps. The second cut is made by a complex of proteins called gamma-secretase. Previous research has identified what are believed to be the main components of this complex. However, researchers have limited information about other proteins in the complex or proteins that regulate gamma-secretase activity.

This investigation will use Drosophila, or the fruit fly, one of the standard workhorses of genetics research. Fruit flies have naturally occurring gamma-secretase. Because this protein complex is present in nerve tissues in the fruit fly eye, the eyes can function as a “reporter” of levels of gamma-secretase.

The researchers will conduct tests that screen for genes that are linked to enhancement or suppression gamma-secretase activity. They hope to isolate these genes and study the characteristics of the proteins that the genes encode. They will concentrate on those genes that have corresponding genes in the human body.

Their immediate goal is to determine the regulatory function of these genes and their protein products. A long-term goal is to determine whether any of the genes are associated with a susceptibility or resistance to Alzheimer’s disease and whether any of them are valid targets for drug therapies to inhibit the production of beta-amyloid.