To view an abstract, select an author from the vertical list on the left.
2007 Grant - Wen
Regulation of APP Processing by Src Family Tyrosine Protein Kinase
Yi Wen, Ph.D.
Columbia University Medical Center
New York, New York
2007 New Investigator Research Grant
One of the hallmarks of Alzheimer's disease is the accumulation of a protein fragment called beta-amyloid. This fragment is suspected of disrupting cell-to-cell communication and causing nerve cell death in the brain. Beta-amyloid is clipped from amyloid precursor protein (APP) by the sequential action of two cutting enzymes called beta-secretase and gamma-secretase. However a third called alpha-secretase, may prevent beta-amyloid formation by cutting up APP before beta-secretase and gamma-secretase can perform their actions.
Scientists believe that alpha-secretase may provide an important therapeutic strategy for Alzheimer's disease. Yet they know little about the exact structural make-up of this enzyme or the biological mechanisms underlying its activities.
Yi Wen, Ph.D., and colleagues have found that proteins called Src kinases help facilitate the clipping of beta-amyloid from APP. In preliminary studies, the researchers used certain molecules to inhibit the activities of Src kinases in nerve cell cultures. This experiment both induced the cleavage of APP by alpha-secretase and reduced production of beta-amyloid.
For their proposed grant, Dr. Wen and colleagues will conduct similar experiments with mice genetically engineered to develop an Alzheimer-like pathology. They hope to confirm that Src kinases block the actions of alpha-secretase and promote beta-amyloid production.
Results of Dr. Wen's study should provide a better understanding of how the production of beta-amyloid is regulated and whether boosting alpha-secretase function is a valid therapeutic strategy.