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2007 Grant - Li
Beta-Amyloid Elicits Its Neurotoxicity by Activating Fyn/c-Cbl Pathway
Zaibo Li, Ph.D., M.D.
University of Rochester
Rochester, New York
2007 New Investigator Research Grant
Beta-amyloid is a protein fragment that is a key pathologic feature of Alzheimer's disease and is toxic to nerve cells in the brain. However, the mechanism by which beta-amyloid exerts its toxicity is not clear, although it is known to increase oxidative stress in brain cells—cellular damage caused by toxic oxygen molecules.
Dr. Zaibo Li and colleagues have recently discovered a cellular signaling pathway—a complex protein chain of command—through which oxidative stress may lead to cell death in Alzheimer's disease. The researchers found that chemically induced oxidative stress in experiments with cell cultures activated a protein known as Fyn kinase. Activation of Fyn caused activation of downstream signaling pathways, eventually leading to the disruption of proteins known as receptor tyrosine kinases (RTKs), which are important for controlling cell growth and survival.
Dr. Li and colleagues plan to test whether beta-amyloid-mediated oxidative stress activates the Fyn pathway in brain cells. They will also study the cells to see if such activation leads to the disruption of RTK signaling pathways that are important for cell survival. These studies will be performed in cultured brain cells, as well as in mice carrying genetic alterations that make them a good model for Alzheimer's disease. The researchers will also search for treatment interventions that prevent the toxicity caused by beta-amyloid. These studies may lead to the identification of new therapeutic targets for treating Alzheimer's disease.