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2013 Grants - DeMartino
Dysfunctional Arc Proteostasis in Alzheimer's Disease Pathogenesis
George N. DeMartino, Ph.D.
University of Texas Southwestern Medical Center
2013 Investigator-Initiated Research Grant
One of the earliest changes that occurs in the brain at the onset of Alzheimer's disease is a decline in synaptic signaling. Synapses are specialized connections between nerve cells that allow the brain to rapidly process information, and which are essential for many of the brain's unique capabilities, including learning and memory.
For synapses to function properly, one nerve cell must maintain proteins on the cell surface that serve as docking sites for chemicals released from other nearby nerve cells. In the early stages of synapse loss in Alzheimer's disease, these proteins, known as receptors, are taken up into the cell, making them unavailable for synaptic signaling between cells.
George N. DeMartino, Ph.D., and colleagues have been studying the process by which receptors are taken up into nerve cells—a process known as endocytosis. They have proposed a series of experiments designed to understand the role of another protein Arc (activity-regulated cytoskeleton-associated protein) in the endocytosis of nerve cell receptors at the synapse. The researchers will also study how the protein fragment beta-amyloid disrupts the normal functioning of this system. Beta-amyloid has been implicated in the damage to synapses and nerve cells in Alzheimer's disease and is the protein that primarily makes up plaques, a hallmark of Alzheimer's disease. These studies will improve our understanding of the molecular mechanisms involved in one of the earliest steps of Alzheimer's disease, and they may uncover clues about ways to slow or prevent loss of synaptic function.