2008 Grants - Kaeberlein

TOR Signaling in Beta-Amyloid Toxicity

Matt Kaeberlein, Ph.D.
University of Washington
Seattle, Washington

2008 Investigator-Initiated Research Grant

Beta-amyloid is a protein fragment believed to be a key toxic factor contributing to the dysfunction and loss of brain cells in Alzheimer's disease. Researchers are interested in describing the exact molecular processes of amyloid toxicity and identifying molecules involved in beta-amyloid's function. A better understanding of these details may suggest new therapeutic strategies for treating Alzheimer's disease.

Matt Kaeberlein, Ph.D., and colleagues have been studying the function of an enzyme known as target of rapamycin (TOR) kinase. Studies indicate that its functions in the cell include the regulation of multiple processes in response to nutrients.

Dr. Kaeberlein is now investigating the role of TOR in C. elegans (roundworm) colonies that have been genetically altered to produce human beta-amyloid. The investigators have observed that the inhibition of TOR activity reduces the toxic effect of beta-amyloid on roundworms.

In this study, the team has proposed a series of experiments to characterize the molecular mechanism by which TOR inhibition suppresses beta-amyloid toxicity. This work may indicate whether TOR or a related molecule is a viable target for a disease-modifying treatment.