Employees – University of Copenhagen

Charlotte Stenum-Berg

Charlotte Stenum-Berg


Current research

AMPA receptors are ligand-gated ion channels that open upon binding of the neurotransmitter L-glutamate. AMPA receptors are widely expressed throughout the CNS, where they are crucial for normal brain function and suspected to be involved in a number of CNS diseases such as Alzheimer's, Parkinson's, schizophrenia, major depression, and epilepsy. Recently, the first AMPA receptor targeting drug, perampanel, Fycompa (R), was approved for clinical use in the treatment of epilepsy.

Perampanel belongs to the pharmacological class of negative allosteric modulators (NAMs), which non-competitively down-regulate the AMPA receptor response to L-glutamate. Currently, very little is known about the NAM binding site targeted by perampanel and the molecular mechanisms of NAM function. The aim of my PhD project is to characterize the interactions between NAMs and AMPA receptors in atomic detail with possible implications for future drug design targeting AMPA receptors.

The project involves systematic creation of a library of glycine point mutations within the AMPA receptor, a novel enzyme-based high-throughput assay for surface expression in HEK293 cells, a fluorescent intracellular calcium dye, electrophysiological measurements in Xenopus oocytes, and molecular modeling docking studies.

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