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

Principal Investigator
Chien-Liang Lin, PhD
The Ohio State University Research Foundation
Columbus, OH, USA
About the Research Project
Program
Award Type
Standard
Award Amount
$250,000
Active Dates
July 01, 2014 - June 30, 2017
Grant ID
A2014315S
Goals
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.
Summary
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.
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