Drug Discovery

Neuroprotection

Structural-based Functional Design of Agonists and Antagonists for AMPA-Subtype Glutamate Receptors

Investigator(s): Ming-Ming Zhou, Ph.D., Assistant Professor

Institution(s): Department of Physiology and Biophysics Mount Sinai School of Medicine, New York, NY

Duration: 2000 - 2002

Summary:

The grant will fund a new drug discovery program for compounds to target AMPA glutamate receptors. Glutamate (a brain chemical) plays an important role in learning and memory and also in neurodegeneration (neuronal death). It is important to maintain balance in brain glutamate activity to allow normal cognition but prevent over-activity which causes neuronal death. Glutamate receptors are responsible for regulating brain glutamate activity by controlling calcium levels within cells. This program aims to develop compounds that target a specific AMPA glutamate receptor type called the GluR2 receptor, which regulates glutamate activity. Dr. Zhou will be assisted in his research efforts by Dr. Harel Weinstein, a computational chemist and chairman of the Physiology and Biophysics Department, and Dr. John Morrison a glutamate receptor expert at Mount Sinai who will serve as a consultant. New compounds will be identified from a library of molecules and will be tested for their ability to bind to the GluR2 receptor using a novel and advanced system recently developed by the Mount Sinai team employing nuclear magnetic resonance spectroscopy. Promising compounds will be tested to determine their neurobiological activity. Mount Sinai has provided matching funds to the project as part of its new translational research efforts.