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2012 Grants - Schubert
The Role of the Unfolded Protein Response in Preventing Amyloid Toxicity
David R. Schubert, Ph.D.
Salk Institute for Biological Studies
La Jolla, California
2012 Investigator-Initiated Research Grant
Proteins made inside of cells must be folded to their specific shape before they function properly. A certain percentage of all proteins are unfolded or misfolded, causing the cell to activate a process known as the unfolded protein response, which disposes of these undesirable proteins.
Beta-amyloid is a protein fragment that can aggregate into amyloid plaques, one of the hallmarks of Alzheimer's disease. Cells in the brain work to clear beta-amyloid from the brain, but it is not known whether the unfolded protein response is involved in that process.
David R. Schubert, Ph.D., and colleagues have discovered a new drug candidate, CNB-100, that activates one part of the unfolded protein response and stimulates removal of beta-amyloid from the brain. They have proposed to identify the mechanisms by which CNB-100 activates the unfolded protein response.
The researchers will perform initial experiments in nerve cells growing in culture, but then plan to extend the experiments to animal models. These latter experiments will include studies of how CNB-100 affects the presence of beta-amyloid and amyloid plaques in the brain, as well as how it affects brain function. These studies will begin to address whether CNB-100 is a potential drug candidate for Alzheimer's disease, and may identify other drug targets to improve clearance of beta-amyloid from the brain.