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2007 Grant - Lakshmana
Role of Novel LRP-Binding Proteins on the Amyloidogenic Processing of APP
Madepalli Krishnappa Lakshmana, Ph.D.
University of California
San Diego, California
2007 New Investigator Research Grant
Beta-amyloid is a tiny protein fragment suspected of disrupting cell-to-cell communication and damaging cells in Alzheimer's disease. Beta-amyloid is clipped from a parent molecule called amyloid precursor protein (APP). Increasing evidence suggests that proteins called low-density lipoprotein receptor-related proteins (LRPs) help facilitate beta-amyloid production by interacting with APP. However, scientists do not understand the precise biological mechanisms behind this activity.
In an earlier study, Madepalli Krishnappa Lakshmana, Ph.D., and colleagues found that a section of LRPs called LRP-C37 could, by itself, promote beta-amyloid production in cell cultures. Dr. Lakshmana's team then administered this protein section to yeast cells and identified two other proteins that interacted with the LRP-C37. One of these molecules, called ran-binding protein M, is known to increase secretion of beta-amyloid in cells. The other, snapin, has been shown to increase cellular levels of APP. Such results led the research team to hypothesize that the binding of these two proteins to LRP affects the metabolism of APP and, possibly, the production of beta-amyloid.
For this proposed grant, Dr. Lakshmana's team will conduct a more thorough study to test their hypothesis. Results could lead to new therapeutic strategies for reducing beta-amyloid production in Alzheimer's disease.