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2007 Grant - Geula
Calbindin, Aging and Vulnerability of Cholinergic Neurons to Degeneration
Changiz Geula, Ph.D.
Feinberg School of Medicine
Candidate 2007 Zenith Fellows Award
In Alzheimer's disease and other degenerative brain diseases, some types of nerve cells are more vulnerable to degeneration than others. Nerve cells known as the basal forebrain cholinergic neurons (BFCN) are especially vulnerable. These cells are known to be important for memory and attention, both of which decline in patients with Alzheimer's disease.
Calbindin is a protein found inside nerve cells that binds to calcium. It protects nerve cells from abnormal increases in calcium, which can cause degeneration of the cell. Changiz Geula, Ph.D., and colleagues have found that the levels of calbindin decline in BFCN cells during normal aging. They theorize that such declines may leave the cells vulnerable to degeneration caused by abnormally high calcium levels.
Dr. Geula and colleagues plan to study the role of calbinin in Alzheimer's disease using two approaches. In the first approach, they will study the levels of calbindin in the BFCN cells that remain in individuals affected by Alzheimer's disease. They propose to study whether these nerve cells survived because of the retained the ability to express sufficient calbindin. In the second approach, the researchers will use genetic methods to increase the expression of calbindin in BFCN cells growing in culture. Using this model system, they will test whether calbindin makes the cells more resistant to calcium-induced degeneration.
These studies may shed light on why some nerve cells are more vulnerable than others in persons with Alzheimer's disease. They may also improve our understanding of the molecular mechanisms that determine such vulnerability.