Translational Activators of Glial Glutamate Transporter EAAT2
The most abundant neurotransmitter in the central nervous system is glutamate. The role of this neurotransmitter is to send excitiatory signals to aid in modulation of normal brain function. However, abnormal release of glutamate can overstimulate the neuronal system, resulting in excitoxicty. Glu…
The most abundant neurotransmitter in the central nervous system is glutamate. The role of this neurotransmitter is to send excitiatory signals to aid in modulation of normal brain function. However, abnormal release of glutamate can overstimulate the neuronal system, resulting in excitoxicty. Glutamate-mediated excitoxicity is involved in many neurological disorders, such as epilepsy, stroke, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). Currently available drugs for the prevention of excitoxicity are not very effective and can produce detrimental side effects. The interplay between glutamate release and clearance is controlled, in large part, by the glial glutamate transporter, EAAT2. Thus, drugs that are able to control the activation of EAAT2 provide a novel and promising direction for development of therapeutics for neurodegenerative diseases.
The Ohio State University researchers, led by Dr. Chien-Liang Lin and in partnership with Brigham and Women's Hospital, have developed an approach for preventing glutamate-mediated excitotoxicity. This technology is a series of novel small molecules that enhance the glutamate uptake function through expression of an excitatory amino acid transporters, EAAT2, which causes the glutamate to be removed from the synaptic cleft. The way of enhancing the EAAT2 expression is through translational activation. These drugs provide a novel alternative to traditional therapeutics and hold promise for treatment of neurological diseases such as ALS.
- Therapeutic drugs to treat neurodegenerative disorders
- Enhances glutamate uptake function which allows glutamate to be removed from synaptic cleft
- Therapeutic effect in several animal models of diseases including ALS, epilepsy, Alzheimer's disease, and focal cerebral ischemia