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2010 Grants - Perry
The Role of PGC-1alpha in Alzheimer's Disease
George Perry, Ph.D.
Case Western Reserve University
San Antonio, Texas
2010 Investigator-Initiated Research Grant
PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha) is a protein that regulates energy use in cells. It performs this function by controlling the expression of numerous other proteins involved in energy metabolism. PGC-1alpha also reduces oxidative stress in cells. These functions of PGC-1alpha are known to be deficient in the brains of persons with Alzheimer's disease.
George Perry, Ph.D., and colleagues are studying the role of PGC-1alpha in Alzheimer's disease. Their preliminary results suggest that levels of PGC-1alpha decline in persons with the disease. The researchers have proposed to study the causes of decreased PGC-1alpha, including the possibility that its expression is inhibited by beta-amyloid, a protein fragment at the focus of research into the causes of Alzheimer's disease. Dr. Perry's team will also study how reduced expression of PGC-1alpha affects the progression of disease in mice that have been genetically altered to express Alzheimer-like pathology. Finally, the researchers will study if declines in PCG-1alpha expression in the brain follow patterns similar to patterns of nerve cell loss. These studies will test an important concept about the possible causes of neurodegeneration in Alzheimer's disease, and may lead to the identification of new drug targets.