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2005 Grant - Wang

High-Resolution NMR of ABAD-Abeta Interaction

Chunyu Wang, M.D., Ph.D.
Rensselaer Polytechnic Institute
Troy, New York

2005 New Investigator Research Grant

Researchers have long suspected that the tiny beta-amyloid protein fragment has a toxic effect on cells in the Alzheimer brain. The exact means by which beta-amyloid damages cellular structures or disrupts normal cellular function is not clear.

Recent evidence suggests that beta-amyloid interacts with a molecule called Abeta-binding alcohol dehydrogenase (ABAD). ABAD plays an important role in mitochondria, the energy-producing structures in cells. When beta-amyloid interacts with ABAD, the molecule's normal work may be blocked, possibly resulting in mitochondrial dysfunction and triggering other potentially toxic events in a cell.

Chunyu Wang, M.D., Ph.D., and colleagues are using a nuclear magnetic resonance (NMR) technology that will enable them to produce atomic-
level, high-resolution images of beta-amyloid and ABAD. This may reveal properties of both molecules that cause each one to bind to the other.

The data from the investigation may provide valuable information for a "made-from-scratch" approach to design a therapeutic compound that thwarts the ABAD–beta-amyloid interaction and prevents subsequent toxic events. The work may, therefore, lay the foundation for a disease-modifying therapy addressing a relatively early stage of the Alzheimer's disease process.