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2007 Grant - Lin
Glial Glutamate Transporter EAAT2 as a Potential Therapeutic Target
Chien-liang Glenn Lin, Ph.D.
Ohio State University Research Foundation
2007 Investigator-Initiated Research Grant
Glutamate is a natural neurotransmitter, or chemical messenger, that is essential for normal brain function. But too much glutamate can overexcite neurons and even cause them to die. Such "excitotoxicity" has been postulated to play a role in Alzheimer's disease. This glutamate toxicity may also be exacerbated if non-neuron brain cells, or glia, fail to mop up excess glutamate in the brain.
Chien-liang Lin, Ph.D., and colleagues plan to test this theory by seeing if they can reduce Alzheimer-like pathology by stimulating glutamate uptake by glia. Since these cells produce a specific glutamate transporter, EAAT2, which is instrumental in removing glutamate, the researchers will take advantage of a genetically engineered strain of mice that produce more EAAT2.
Lin and colleagues will cross breed these EAAT2 mice with others that overproduce beta-amyloid precursor protein (APP), the parent molecule of beta-amyloid, a small fragment suspected of disrupting cell-to-cell communication in the brain of those with Alzheimer's. If the excitotoxicity theory is correct, offspring that harbor both genes should have less pathology than those with just the APP gene alone. The researchers will also attempt to address the role of glutamate excitotoxicity in APP mice by administering drugs known to induce production of endogenous EAAT2. This work may help scientists understand the role of glutamate excitotoxicity in Alzheimer's disease, and may help identify potential therapeutic targets.