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2013 Grants - Vassar
Identifying Novel BACE1 Substrates and Interacting Proteins in the Brain
Robert Vassar, Ph.D.
2013 Zenith Fellows Award
Beta-secretase (BACE1) is an enzyme under study as a potential target for drugs to treat Alzheimer's disease. BACE1 begins the production process for beta-amyloid, a protein fragment that is strongly implicated in Alzheimer's disease. However, BACE1 also performs other functions by processing and interacting with other proteins.
Drugs that inhibit BACE1 have been developed and proposed as potential treatments for Alzheimer's disease. Because BACE1 has numerous functions and interactions, however, those drugs have many side effects. At this time, we have limited knowledge about the proteins that BACE1 processes and with which it interacts.
Robert J. Vassar, Ph.D., and colleagues have proposed studies to identify proteins that BACE1 processes and interacts with in the brain. For these studies, they will use a strain of mice that have been genetically engineered to have a mutant form of BACE1. This mutant BACE1 binds to proteins in its usual manner, but does not process them. Furthermore, the binding is permanent. This permanence allows the researchers to identify proteins that interact with BACE1 by extracting BACE1 itself from brain tissue. Dr. Vassar's team can then use biochemical techniques to identify the proteins bound to BACE1.
After identifying BACE1-interacting proteins, the researchers will begin studies in cells to determine how normal BACE1 processes the proteins or interacts with them. These studies will provide valuable information about the various roles of BACE1, and may allow the future design of drugs that inhibit only beta-amyloid processing and potentially have fewer side effects.