Dongxu Zhai, Shuxin Yan, James Samsom, Le Wang, Ping Su, Anlong Jiang, Haorui Zhang, Zhengping Jia, Izhar Wallach, Abraham Heifets, Chiara Zanato, Chih-Chung Tseng, Albert H C Wong, Iain R Greig, Fang Liu
While most research and treatments for multiple sclerosis (MS) focus on autoimmune reactions causing demyelination, it is possible that neurodegeneration precedes the autoimmune response. Hence, glutamate receptor antagonists preventing excitotoxicity showed promise in MS animal models, though blocking glutamate signaling prevents critical neuronal functions. This study reports the discovery of a small molecule that prevents AMPA-mediated excitotoxicity by targeting an allosteric binding site. A machine learning approach was used to screen for small molecules targeting the AMPA receptor GluA2 subunit...
December 8, 2023: Science Advances