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2008 Grants - Annaert
Targeting and Localization of Distinct Gamma-Secretase Complexes Versus APP
Willem Godfried Annaert, Ph.D.
Flanders Interuniversity Institute for Biotechnology
2008 Investigator-Initiated Research Grant
The protein fragment beta-amyloid may disrupt cell-to-cell communication and promote cell death in Alzheimer's disease. Beta-amyloid is clipped from its parent molecule, amyloid precursor protein (APP), in a two-stage process. During the second stage, the fragment is released by a protein complex known as gamma-secretase. Gamma-secretase also processes other proteins, including Notch, that may play important roles in nerve cell development. However, scientists do not know exactly how or why gamma-secretase targets different molecules.
Current research has found that a single neuron may contain diverse types of gamma-secretase complexes. Variations in gamma-secretase involve differences in presenilin genes and other key secretase components. One form of the presenilin gene, known as presenilin-1, tends to become mutated in people who acquire the familial (inherited) form of Alzheimer's. Scientists believe that different varieties of gamma-secretase may target different proteins.
For their proposed study, Willem Godfried Annaert, Ph.D., and colleagues hope to determine more precisely which forms of gamma-secretase target APP, Notch and other Alzheimer-related molecules. They also hope to learn more about the biological mechanisms underlying such interactions. For this effort, the team will use cultured cells and a high-resolution imaging technique. Results of the study could lead to better methods of preventing or reversing Alzheimer-related protein build-up in the brain.