

Glutamate, the main excitatory neurotransmitter in the central nervous system, is involved in cognitive functions such as learning and memory. Excitatory amino acid transporters (EAATs) present on the plasma membrane regulate and modulate glutamate neurotransmission by taking up released glutamate from the extracellular space back into neurons and glial cells. Thus, these transporters have an essential role of maintaining extracellular glutamate concentrations below neurotoxic levels.

Pathologically high levels of extracellular glutamate can cause excitotoxicity, when postsynaptic receptors such as NMDA and AMPA are overactivated, allowing high levels of calcium influx that trigger a number of biochemical cascades and ultimately cell death.

Excitotoxicity plays a role in several neurological disorders, such as traumatic brain injury (TBI), stroke, epilepsy, amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), Alzheimer’s disease, Huntington’s disease, HIV-associated neurocognitive disorders (HAND) and neuropathic pain, among others. Additionally, dysregulation in glutamatergic signaling has been implicated in mental health and substance use disorders.

Yet there are no therapies that limit secondary injury due to excess glutamate. The glial glutamate transporters EAAT1 and 2 play major roles in glutamate clearance. Thus, development of pharmacologic approaches to augment EAAT activity could lead to improved treatments for these conditions.

In this regard, our lab is interested in furthering the knowledge of mechanisms for regulation and modulation of glutamate transporters. Such knowledge can lead to the development of translational approaches for many CNS disorders; therefore we also develop translational projects to evaluate these compounds in in vitro and in vivo models.

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