2004 Investigator-Initiated Research Grant

Cell-to-cell communication in the brain depends on the sending and receiving of messenger chemicals. Receptors on a cell surface are “docking sites” for receiving messengers. A receptor, in turn, can activate molecules responsible for turning on and off chains of command that govern important cellular activities. This complex system of signals affects how memory is built, how messengers are sent, and how a cell maintains itself.

Research has demonstrated that a tiny protein fragment called beta-amyloid may somehow disrupt cell-to-cell communication and induce cell death. Studies have also shown that overactivation of the NMDA receptor, a docking site for the memory-related messenger chemical glutamate, results in the death of nerve cells.

Michal Hetman, M.D., Ph.D., and colleagues are examining the role of NMDA receptors in Alzheimer-related cellular events and their possible contribution to beta-amyloid toxicity. The researchers have hypothesized that excessive activation of NMDA receptors sets in motion a chain of molecular events that prevents the “switching on” of a gene essential for cell survival.

In this study, the investigators will use brain cells from rats to test this hypothesis. They will characterize the steps of this suspect chain of command and investigate a possible cooperation between NMDA receptors and beta-amyloid in the regulation of these events. The outcome of this work may help clarify molecular-level processes in Alzheimer’s disease and suggest new targets for developing disease-modifying drugs.