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2007 Grant - Dineley
Alpha7 nAChR Protects Against Beta-Amyloid Toxicity in Vivo
Kelly Dineley, Ph.D.
University of Texas Medical Branch
2007 Investigator-Initiated Research Grant
Alzheimer's disease is characterized by the degeneration and eventual death of specific types of brain cells known as cholinergic neurons. These neurons use a chemical messenger called acetylcholine to communicate with one another and with other cells. Acetylcholine binds to specific receptors, or "docking sites," on the neurons. One particular group of docking sites, the nicotinic acetylcholine receptors (nAChRs), has been linked to Alzheimer's disease. People with the disease have lost some of their nAChRs.
Previous research has shown that the stimulation of one type of nAChR, called alpha7 nAChR, can help strengthen the cholinergic system. This receptor has also been shown to prevent build-up of the protein fragment beta-amyloid, a key suspect in Alzheimer's. In a preliminary study, Kelly Dineley, Ph.D., and colleagues developed a mouse model that lacked alpha7 nAChR. Results found that these mice suffered (1) damaged cholinergic systems; (2) shrinkage of the hippocampus, a region of the brain important for learning and memory; and (3) loss of cognitive function at much earlier ages than did other mice. Interestingly, the mice also showed lower levels of beta-amyloid in some brain regions.
For this proposed grant, Dr. Dineley's team will conduct a more thorough study to confirm the findings of their earlier research. Results could shed new light on how alpha7 nAChR protects the cholinergic system and the general health of the brain. The study should also determine what role, if any, this receptor may play in beta-amyloid accumulation.