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 over activated—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), Alzheimer's disease, Huntington's disease, HIV-associated neurocognitive disorders (HAND), among others.
Therefore, potential ways to prevent or treat excitotoxicity include increasing glutamate clearance by activating glutamate transporters. In this regard, our lab is interested in furthering the knowledge of mechanisms for regulation of glutamate transporters and developing such approaches for neuroprotection.
Current projects in the lab include the identification and development of allosteric compounds that enhance the activity of EAAT2 (the main glutamate transporter in the brain) and the examination of potential neuroprotection of these compounds in in vitro and in vivo models.
In addition, our lab is interested in mechanisms involved in transport augmentation that could lead to therapies to treat disorders in which excitotoxicity is involved.
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