2005 Investigator-Initiated Research Grant

A neuron has tiny pores, or channels, in its membrane that regulate the flow of ions, or electrically charged chemical particles, into and out of the cell. This activity is a function of the nervous system’s communication network.

A key feature of Alzheimer’s disease is the accumulation of a tiny protein fragment called beta-amyloid. Although there is much evidence that beta-amyloid is a key toxic factor in the disease, its mechanism of action is not well understood. One hypothesis suggests that beta-amyloid creates abnormal ion channels in the membrane of neurons. This “unregulated leaking” of ions would alter the properties and function of a cell.

Bruce L. Kagan, M.D., Ph.D., and colleagues are using a technology that enables the rapid screening of compounds for their ability to block beta-amyloid ion channels. They aim to screen drugs already approved by the Food and Drug Administration and other compounds for their channel-blocking potential. The investigators will assess the effect of the most promising compounds in rats with beta-amyloid–induced brain dysfunction. The outcome of this work may demonstrate the utility of such compounds to block amyloid toxicity and lay the groundwork for future clinical studies.