Regulating Glutamate Levels as a Therapeutic Strategy for AD

Chien-liang Lin, PhD
The Ohio State University Research Foundation (Columbus, OH)
Year Awarded:
Grant Duration:
July 1, 2014 to June 30, 2017
Award Amount:
Grant Reference ID:
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Award Region:
US Midwestern

A New Method to Reduce Alzheimer Phenotypes by Increasing Glutamate Transporter Expression


The glial glutamate transporter, EAAT2, is responsible for maintaining low extracellular glutamate concentrations in our brains. Loss of EAAT2 protein and function is commonly found in patients with Alzheimer's disease. We previously discovered that restoration of EAAT2 function can reverse Alzheimer phenotypes in an animal model of Alzheimer's disease. The goal of this research is to develop restoration of EAAT2 function as a therapeutic strategy for Alzheimer's disease.


The glutamate transporter, EAAT2, plays a critical role in cognitive functions and the homeostatic regulation of extracellular glutamate levels in the central nervous system. Loss of EAAT2 protein is a common phenomenon observed in Alzheimer’s disease (AD) patients and animal models. Recently, we found that restoring EAAT2 protein function using a novel drug-like compound, which we previously identified, significantly improved learning/memory and reduced Alzheimer’s pathology in a mouse model of AD. Importantly, the observed benefits were sustained one month following compound treatment cessation, suggesting that EAAT2 is a disease modifier. Thus, our EAAT2 enhancing compound has therapeutic potential for AD. Our current research aims to investigate the underlying mechanisms by which increased EAAT2 reverses Alzheimer phenotypes in an AD mouse model. Secondly, we aim to investigate the detailed mechanisms of how our drug-like compound restores EAAT2 function. This study presents a new and promising approach for AD treatment. Results from this study can provide critical information regarding a novel method of restoring cognitive functions in AD and contribute to the potential development of our compound for human use.

About the Researcher

C. Glenn Lin completed his doctorate in molecular biology and biochemistry at the Johns Hopkins University in 1995. He performed postdoctoral research in the Department of Neurology at the Johns Hopkins University. Dr. Lin joined the Department of Neuroscience at the Ohio State University in 1999, where he directed his research to molecular mechanisms underlying neurodegenerative diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and epilepsy. His recent research focuses on the role of glutamate transporter EAAT2 in the regulation of synaptic plasticity and function and in the pathogenesis of neurodegenerative diseases. He has published numerous papers in major journals and holds four patents.