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2005 Grant - Li
Function of APL-1, an APP-Related Protein in C. Elegans
Christine Li, Ph.D.
City College of New York and the Research Foundation
City University of New York
New York, New York
2005 Investigator-Initiated Research Grant
Beta-amyloid, a key suspect in Alzheimer's disease pathology, is a tiny fragment clipped from the larger amyloid precursor protein (APP). Although the process of cleaving APP is generally well understood, the normal role of APP in humans is uncertain. Without this knowledge, developing therapeutic strategies that target the regulation of APP are difficult to formulate.
APP-related genes have been found in diverse organisms, including flies, worms, rodents and primates. The structure of the proteins produced by these genes has changed little through evolution, suggesting that their functions are likely to be similar. Flies in which an APP-related gene has been inactivated show behavioral defects. These defects can be partially reversed by the introduction of a human APP gene, demonstrating that the protein products of these two genes are functionally similar. Because genetic and molecular manipulations are easier and more feasible to perform in simple organisms (such as flies and worms) than in complex organisms (such as mammals), the simple organisms provide a useful model for understanding the normal function of APP in humans.
The aim of this project by Christine Li, Ph.D., and colleagues is to examine an APP-related gene in the roundworm Caenorhabditis elegans. Preliminary studies demonstrated that both a lack of the APP-related gene or overactiva-tion of the gene causes the worm to die. This suggests that the gene is both essential and carefully regulated. The current work will involve a series of experiments that alter the APP-related gene in ways that enable the investigators to tease out its function in the C. elegans nervous system. Findings may lay the groundwork for understanding the normal function of APP in humans.