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2007 Grant - S. Lee
A Novel Transgenic Model for Alzheimer's Disease
Hyoung-gon Lee, Ph.D.
Case Western Reserve University
2007 New Investigator Research Grant
Cells in many parts of the body reproduce themselves by cell division throughout the life of the organism. While some new cell growth occurs in the adult brain, mature brain cells usually die when they are induced to divide. Studies have shown, however, that brain cells attempting to divide are much more common in Alzheimer's disease. These observations suggest that the cell death seen in Alzheimer's may arise from unknown signals that stimulate brain cells to divide. However, the association between cell division and Alzheimer pathology is not well understood.
In preliminary experiments, Hyoung-gon Lee, Ph.D., and colleagues have identified a protein that induces brain cells to enter the cell division cycle. This protein is encoded by MYC, a gene that also is associated with numerous cancers. Moreover, the team found that MYC-induced cell division led to the production of abnormal tau protein. Abnormal tau tends to form tangles that represent a key hallmark of Alzheimer's disease. To further study the effects of MYC, Dr. Lee's team developed a mouse model that produced MYC protein in the forebrain. Researchers found that the protein drove forebrain brain cells in the mice to enter the cell division cycle, which initiated the production of abnormal tau.
For this proposed grant, Dr. Lee's team will conduct more thorough studies of their mice to understand the biological mechanisms behind MYC-induced brain cell division. Results could lead to novel therapies for preventing brain cell death in Alzheimer's disease.