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2008 Grants - Shi
Oxidative Stress/Gene Regulation of Mitochondrial Enzymes Implicated in Alzheimer's Disease
Qingli Shi, Ph.D.
Winifred Masterson Burke Medical Research Institute
White Plains, New York
2008 New Investigator Research Grant
Oxidative stress involves damage to cellular structures caused by free radicals, or toxic oxygen molecules. Free radicals are normal byproducts of cellular activities, and the body's natural defenses normally hold them in check. However, these defenses appear to decline with age, and oxidative stress may contribute to cell damage in Alzheimer's disease. Many investigators are studying the precise biological mechanisms behind oxidative stress and its effects on the Alzheimer brain.
In preliminary research, Qingli Shi, Ph.D., and colleagues have found that Alzheimer-related oxidative stress alters the transcription, or "activation," of certain enzymes from the genes that encode them. These enzymes exist in mitochondria, cellular structures that use oxygen and nutrients to produce energy for a cell. The enzymes are involved in a process called the tricarboxylic acid (TCA) cycle. Altered TCA cycle enzymes may inhibit the TCA cycle process and reduce the brain's ability to break down harmful Alzheimer-related molecules.
For this study, Dr. Shi's team plans to determine whether oxidative stress promotes Alzheimer development by altering the transcription of TCA enzymes. Using sophisticated genetic analysis techniques, the researchers will study TCA transcription abnormalities in cultured cells and in animals engineered to develop oxidative stress.
The results of Dr. Shi's study could shed new light on the genetic mechanisms underlying early Alzheimer's disease. Such knowledge may lead to novel therapies for the disease.