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2011 Grants - Mura
Mechanisms of the Neuromodulatory Action of Beta-Amyloid
Elisa Mura, Ph.D.
University of Pavia
2011 New Investigator Research Grant
Accumulations of the protein fragment beta-amyloid, a key suspect in Alzheimer's disease, have been shown to inhibit the ability of brain cells to communicate with one another. This inhibition may lead to brain cell death in the disease. Many research teams have been studying how beta-amyloid may exert its toxicity, especially in the earliest stages of Alzheimer's.
Based on preliminary studies, Elisa Mura, Ph.D., and colleagues have found that beta-amyloid may affect the release and function of chemical messengers called neurotransmitters. Nerve cells communicate by sending neurotransmitters to neighboring cells through tiny junctions known as synapses. The researchers hypothesize that these small amyloid-induced changes to neurotransmitters may lead to synaptic damage and eventually compromise the entire cell-to-cell communication system in the brain.
For their current study, Dr. Mura and colleagues will expand on their earlier studies. Using laboratory cells and animal models, they will analyze the ability of beta-amyloid to modulate the release of three neurotransmitters —glutamate, GABA and aspartate — in the hippocampus, a brain region affected early in Alzheimer's. They will also assess whether the receptors, or cellular "docking sites," for these messenger chemicals are affected by beta-amyloid. The researchers hope to identify a mechanism by which beta-amyloid begins its "assault" on the brain's learning and memory functions. This research could lead to therapies that prevent the development of Alzheimer's and other dementias.