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2014 Grants - Tomaselli
Structural Insights on Oligomers of Abeta Peptides in the Presence of PrPC
Simona Tomaselli, Ph.D.
CNR Institute for Macromolecular Studies
2014 New Investigator Research Grant
Abeta (also known as beta-amyloid) is a protein fragment thought to play an important role in the development of Alzheimer’s disease. Beta-amyloid is the main component of amyloid plaques, a hallmark of Alzheimer’s disease in the brain. Before it clumps into plaques, beta-amyloid forms smaller aggregates, known as oligomers, composed of only a few beta-amyloid molecules. Oligomers may account for much of the toxicity of beta-amyloid in Alzheimer’s disease. However, the first steps in the formation of oligomers and how they affect nerve cell function are not yet well understood.
Simona Tomaselli, Ph.D., and colleagues have proposed a series of studies using sophisticated biochemical methods to explore how the beta-amyloid oligomers form. They plan to combine different versions of beta-amyloid protein fragments known to play a role in Alzheimer’s disease, and determine what amounts and combinations lead to formation of oligomers. Recent studies have also provided evidence that beta-amyloid oligomers can bind to a protein known as cellular prion protein (PrPC), which is implicated in several forms of brain degeneration. Dr. Tomaselli and colleagues will study how beta-amyloid binds to PrPC and how that interaction affects the formation of oligomers and alters brain cell function.
These studies may reveal valuable insights into the molecular mechanisms of oligomer formation, and how they may contribute to the brain changes associated with Alzheimer’s disease.