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2011 Grants - Castaño
Neuronal Vulnerability to Amyloid Peptides: From Drosophila to Human Brain
Eduardo M. Castaño, M.D.
Leloir Institute Foundation
Buenos Aires, Argentina
2011 Investigator-Initiated Research Grant
During the development and progression of Alzheimer's disease, specific types of nerve cells in the brain are vulnerable to cell death. Although the causes of this selective vulnerability are not well understood, it has been linked with the accumulation of beta-amyloid. Beta-amyloid is a protein fragment (peptide) that aggregates to form amyloid plaques, one of the hallmarks of Alzheimer's pathology.
Eduardo M. Castaño, M.D. and colleagues are studying why some nerve cells are especially vulnerable using the fruit fly Drosophila, a widely used research model. Using molecular genetic techniques, Dr. Castaño and colleagues will develop strains of Drosophila in which overexpression of beta-amyloid (or related protein fragments implicated in other forms of dementia) can be switched on by the researchers at specific times. Using these model organisms, the researchers will identify genes associated with increased vulnerability to cell death in nerve cells exposed to beta-amyloid and other protein fragment. Dr. Castaño's team will then identify the human version of any such genes and examine whether their expression is altered in persons affected by Alzheimer's disease. These studies will advance our understanding of why certain nerve cells are especially vulnerable to death in Alzheimer's disease, and they may suggest ways to develop treatments to prevent such vulnerability.