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2007 Grant - Szalai
Neurotoxicity and Structure of Copper-Containing Beta-Amyloid
Veronika A. Szalai, Ph.D.
University of Maryland
2007 Investigator-Initiated Research Grant
A prime suspect in Alzheimer's disease is a tiny protein fragment called beta-amyloid, which tends to clump together to form abnormal structures called plaques. Although beta-amyloid's exact role in the disease is not known, it is believed to be linked to a breakdown in cell-to-cell communication and the loss of brain cells. A growing number of research teams are studying the structure of beta-amyloid plaques in order to better understand how the protein fragment accumulates and becomes toxic to brain cells.
Various metals — including copper, zinc, and iron — are present in beta-amyloid plaques. Studies have shown that these metals may generate reactive oxygen compounds that cause damage to nerve cells. Veronika A. Szalai, Ph.D., and colleagues are analyzing the chemical processes that may lead to metal-induced cell damage. Their work focuses specifically on copper, which has also been associated with brain cell death in Parkinson's disease and other neurological disorders.
For this proposed grant, Dr. Szalai's team will determine if the process of copper binding to beta-amyloid leads to the creation of toxic beta-amyloid clumps. They will also seek to confirm whether copper-containing beta-amyloid formations generate toxic oxygen compounds. The team's work will involve a thorough analysis of the structure of molecules formed by copper and beta-amyloid.
Results of this study may help identify copper as a key amyloid-binding metal in the development of Alzheimer pathology. If so, Dr. Szalai's work may lead to the development of metal-binding drugs that more effectively reduce toxic beta-amyloid production.