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2011 Grants - Rissman
CRF Receptor Antagonism in Alzheimer's Disease
Robert A. Rissman, Ph.D.
University of California - San Diego
La Jolla, California
2011 New Investigator Research Grant
The beta-amyloid protein fragment and abnormal tau protein are two key suspects in Alzheimer's disease. Both tend to aggregate into clumps in the Alzheimer's brain that hinder cell-to-cell communication and cause brain cell death. Beta-amyloid is produced from a larger molecule called amyloid precursor protein, while toxic tau is produced when normal tau is abnormally modified in a process called hyperphosphorylation. Current research suggests that stress may play a role in promoting Alzheimer's pathologies or brain changes.
In previous studies with rodents, Robert A. Rissman, Ph.D., and colleagues have found that a type of brain protein called corticotropin-releasing factor (CRF), which is produced in response to stress, may play a role in tau hyperphosphorylation. The researchers also found that by reducing the activity of a particular receptor, or "docking site," for CRF, they could dramatically reduce beta-amyloid levels in the animals.
For their current grant, Dr. Rissman and colleagues will use rats to learn more about the mechanisms underlying CRF's role in toxic tau and beta-amyloid production. They will also test various genetic and drug therapies for hindering Alzheimer's-related CRF activities. Results of this research could lead to the use of anti-CRF treatments for dementia in human clinical trials.