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Research Grants - 2006


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Research Grants 2006


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

2006 Grant - Dickey

Tau Therapeutic Strategies for Alzheimer's Disease

Chad Dickey, Ph.D.
Mayo Clinic
Jacksonville, Florida

2006 New Investigator Research Grant

Any protein in the body must "fold" itself into its correct three-dimensional shape in order for it to carry out its function properly. In healthy neurons, the correctly folded tau protein has important functions related to maintaining the cell's structure and transporting nutrients throughout the cell.

In Alzheimer's disease, tau proteins undergo an unchecked chemical change that results in misfolding. These structural changes cause them to lose their normal function and enable them to form abnormal structures called neurofibrillary tangles inside neurons.

One potential treatment strategy to correct problems with misfolded tau proteins is to enhance the function of chaperone proteins. Chaperones help other proteins assume their correct shape, stabilize correctly folded proteins, correct misfolded proteins, or mediate the degradation of misfolded proteins.

In previous studies, Chad Dickey, Ph.D., and colleagues identified compounds-including some that have already been approved for treating other diseases-that induce chaperone production and activity. In this research, they will test these compounds in normal mice to confirm that they induce chaperones that mediate abnormal tau degradation and stabilize normal tau. They will then test the effect of the most promising compounds in genetically altered mice that develop an Alzheimer-like tau pathology.

The investigators will also study the mechanisms by which these chaperones mediate abnormal tau degradation in cell cultures. A better understanding of the mechanisms may help identify the best target for drug therapies. The outcome of this work may provide evidence to develop clinical trials of compounds for disease-modifying therapies.