Seong-Hun Kim, M.D., Ph.D.
University of Chicago
Chicago, Illinois

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 stages, the second of which is carried out by a complex of proteins called gamma-secretase. One specialized field of Alzheimer research is investigating the various protein components of this complex and determining how they interact with each other and how these interactions affect the processing of beta-amyloid.

One of the proteins in the complex is called presenilin 1. It is of particular interest because mutations in the gene that encode the protein cause the rare early-onset form of the disease.

This research group is investigating how PEN-2, one of the other proteins in the gamma-secretase complex, may affect the stabilization and breakdown of presenilin 1 and ultimately the production of beta-amyloid. In studies of cell cultures, the researchers will (1) exam the location of PEN-2 in the cell, (2) analyze the structure and function of PEN-2, and (3) identify other proteins that interact with it. This research may provide insight into the fundamental cellular processes that lead to Alzheimer pathology and suggest new strategies for developing future therapies.