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2006 Grant - Bezprozvanny
Presenilins and Calcium Signaling: Implications for Alzheimer's Disease
Ilya B. Bezprozvanny, Ph.D.
University of Texas Southwestern Medical Center
2006 Investigator-Initiated Research Grant
Mutations in three different genes are known to cause familial Alzheimer's disease, a rare, inherited form of the disease that usually affects middle-aged people. Two of these genes are known as the presenilin genes, PS1 and PS2. Research has shown that PS1 and PS2 mutations may be associated with the inappropriate regulation and storage of calcium in cells. Other studies have shown that impaired regulation of calcium may be implicated in both normal aging of the brain and Alzheimer's disease.
Ilya B. Bezprozvanny, Ph.D., and colleagues hypothesize that the presenilin proteins coded by PS1 and PS2 act as "channels" through which calcium is transported. They also believe that Alzheimer-related PS1 and PS2 mutations impair these proteins' ability to properly transport calcium. To test their hypotheses, Dr. Bezprozvanny's team will use laboratory cells to produce normal PS1 and PS2 genes, as well as the presenilin mutations associated with Alzheimer's. They will then measure and compare the calcium-transporting ability of the normal and mutant presenilins. Researchers also will measure and compare calcium deposits in (1) cells from normal mice, (2) cells from mice genetically altered to lack PS1 and PS2, and (3) mouse cells that have been altered to contain normal and mutant forms of PS1 and PS2.
The results of this work could lead to innovative genetic treatments for familial Alzheimer's disease.