2010 Grants - Lin

Evaluating Glial Glutamate Transporter EAAT2 Activators in APP Mice

Chien-liang Glenn Lin, Ph.D.
Ohio State University
Columbus, Ohio

2010 Investigator-Initiated Research Grant

Nerve cells use chemicals known as neurotransmitters to send rapid signals to neighboring nerve cells. A common neurotransmitter in the brain is glutamate. There is ample evidence, however, that excessive glutamate in the brain is toxic to nerve cells, and excessive glutamate may contribute to Alzheimer pathology.

Chien-liang Glenn Lin, Ph.D., and colleagues are studying one of the mechanisms by which the brain removes glutamate and prevents it from causing nerve cell death. This mechanism is a protein (EAAT2) known as a glutamate transporter. EAAT2 resides in the cell membrane of other cells in the brain known as glial cells, which support many aspects of brain function. Dysfunction of EAAT2 is thought to be an important cause of glutamate toxicity in Alzheimer's disease. Dr. Lin and colleagues have identified drug candidates that increase the expression of EAAT2, possibly restoring it to normal function. They now plan to test whether these drugs can restore the ability of glial cells to remove glutamate from the brain, and reduce nerve cell death in rats that exhibit Alzheimer-like pathology. These studies may identify drug candidates for reducing or halting the development of glutamate toxicity and Alzheimer pathology in the brain.