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2010 Grants - Barbagallo
The Role of APP Phosphorylation Induced by IGF-1 in APP Processing
Alessia Barbagallo, Ph.D.
Albert Einstein College of Medicine at Yeshiva University
Bronx, New York
2010 New Investigator Research Grant
Much Alzheimer research has focused on the protein fragment beta-amlyloid. This fragment, which is clipped from a larger molecule called amyloid precursor protein (APP), accumulates in the Alzheimer brain and may cause nerve cell damage and death. Recent studies, however, have found that APP itself may contribute to Alzheimer pathology in other ways. These studies suggest that APP plays essential roles in brain health, and that alterations in normal APP processing could prevent the protein from carrying out its essential functions.
APP is a transmembrane protein, meaning that part of the molecule resides inside a cell and part resides outside the cell. The part that resides inside the cell, known as intracellular APP, is normally modified by a process called phosphorylation, or the addition of phosphate molecules. Previous studies have found that the phosphorylation of intracellular APP helps regulate normal APP processing. Alessia Barbagallo, Ph.D., and colleagues have identified a protein called insulin-like growth factor 1 (IGF-1), which may play a key role in intracellular APP phosphorylation.
For this proposed study, Dr. Barbagallo's team has engineered mice to develop APP that can become abnormally phosphorylated. Using these animals, the team will assess how abnormal phosphorylation—and the loss of normal IGF-1 activity—may affect APP processing in cells and lead to brain cell damage. This work could reveal new information about the role of APP in the early stages of Alzheimer's and other brain disorders.