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Research Grants 2008

To view an abstract, select an author from the vertical list on the left side.

2008 Grants - Lin

A Novel Mouse Model of Neurodegeneration

David M. Lin, Ph.D.
Cornell University
Ithaca, New York

2008 Investigator-Initiated Research Grant

Alzheimer research has long recognized amyloid precursor protein (APP) as an important factor in Alzheimer's disease. APP is the parent molecule of beta-amyloid, a protein fragment that tends to accumulate into clumps within the Alzheimer brain. Beta-amyloid is clipped from APP in a two-stage process. The second cut is made by the protein complex gamma-secretase. This complex also processes another brain protein called Notch. Because of the relationship between APP and Notch, scientists have long felt that Notch also plays a role in Alzheimer development. Research suggests that the impairment of Notch activities may lead to the degeneration of nerve cells.

In preliminary research with mice, David M. Lin, Ph.D., and colleagues found that receptors, or "docking sites," for Notch occur on the cells of the nasal cavity. Such cells help control the body's sense of smell. When researchers inhibited the ability of Notch to interact with nasal cavity cells, their action caused a decline in the function of glial cells, the helper cells of the brain. These glial cell abnormalities, in turn, led to the degeneration of nerve cells involved in controlling smell.

For their proposed grant, the investigators plan to conduct a similar experiment with Notch receptors on the glial cells of the hippocampus. The hippocampus is an area of the brain important for learning and memory. Dr. Lin and colleagues believe that by inhibiting the ability of Notch to interact with hippocampal glial cells, they can induce the degeneration of these cells. Such degeneration may cause Alzheimer-like damage to hippocampal nerve cells.

Results of Dr. Lin's study could reveal biological mechanisms underlying Notch's role in Alzheimer's. Such knowledge could foster new therapeutic approaches for the disease.

Alzheimer's Association International Conference | July 16-20, 2017, London, England

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