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2010 Grants - Zhang
The Involvement of CutA in Alzheimer's Disease
Yunwu Zhang, Ph.D.
2010 New Investigator Research Grant
One of the hallmark features of Alzheimer pathology is amyloid plaque, which consists largely of the protein fragment beta-amyloid. Because of beta-amyloid's central role in Alzheimer's disease, inhibition of its production is a key goal for drug therapy. A primary target for drug therapy is the enzyme BACE1, which begins the process of producing beta-amyloid by cutting its precursor protein.
Yunwu Zhang, Ph.D., and colleagues have identified a protein that interacts with BACE1, known as CutA. Increased expression of CutA reduces the activity of BACE1 and changes where BACE1 is localized within the cell. Because CutA binds copper atoms, Dr. Zhang and colleagues tested the effects of high copper levels. They found that increased copper levels caused an increase in BACE1 levels.
Dr. Zhang's team plans to study the roles of CutA and copper atoms in the regulation of BACE1 and the production of beta-amyloid. They will extend their studies of how CutA affects the activity and localization of BACE1. The researchers will also examine whether BACE1 levels affect the levels or activity of CutA, including other important functions of this protein. Finally, Dr. Zhang and colleagues will study how copper affects beta-amyloid production and whether such effects are mediated through CutA. These studies will advance our knowledge of key enzymes involved in the development of Alzheimer pathology, and they may answer important questions about the role of copper in the development of disease.