Allosteric Modulation of Glutamate Transporters: A Possible Avenue for Neuropsychiatric Therapies

Wednesday, January 18, 2023

4:00 PM-5:30 PM

BIOMED Seminar

Title:
Allosteric Modulation of Glutamate Transporters: A Possible Avenue for Neuropsychiatric Therapies

Speaker:
Andréia C. K. Mortensen, MSc, PhD
Assistant Professor
Department of Pharmacology and Physiology
Drexel University College of Medicine

Details:
Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS), and it is critically involved in processes such as memory, learning, neurogenesis, among others. Excitatory amino acid transporters, or EAATs, are key proteins in the CNS that remove extra synaptic glutamate and terminate excitatory signals, thereby being extremely important to maintain homeostasis. The astrocytic EAAT2 subtype is the predominant transporters responsible for glutamate clearance.

Elevated concentration of synaptic glutamate is associated with many pathologies, including stroke, epilepsy, and neuropathic pain. Additionally, glutamate plays a central role in processes underlying the development and maintenance of addiction. Unfortunately, there are no safe and effective treatments for these disorders. In our lab, we study the regulation of EAATs in physiological and disease states and aim to target these transporters for drug development. We have identified allosteric modulators of EAATs that activate the function of these transporters, that remove excess glutamate and thereby provide a starting point for therapy development for many disorders. Our preliminary data shows that positive allosteric modulators (PAMs) of EAAT2 offers in vitro neuroprotection after stroke. We have also shown that the levels of astrocytic EAATs vary according to the severity of the stroke insult, and this could have implications for therapy development.

Our future directions are to evaluate the effects of EAAT2 PAMs in an in vivo stroke model. We have also showed that our lead EAAT2 PAM offers antinociception in a neuropathic pain model, and decrease cocaine seeking behavior, suggesting that the development of these novel compounds can be helpful for many of these neuropsychiatric disorders.

Biosketch:
Andreia Mortensen, MSc, PhD, is an Assistant Professor in the Department of Pharmacology and Physiology at Drexel University College of Medicine. She has a PhD in Biochemistry from the University of São Paulo, Brazil, and two postdocs in the areas of Neuroscience and Neurobiology. She is a recipient of an RO1 grant from the National Institute of Neurological Disorders and Stroke (NINDS/NIH). Dr. Mortensen is also the Course Director of Principles of Neuropharmacology, a member of the Society for Neuroscience (SfN), as well as the American Society for Pharmacology and Experimental Therapeutics (ASPET).

Contact Information

Lisa Williams
ltw22@drexel.edu