Neurology

In vitro, cell culture and mouse studies identified a diphenyl-imidazole-based QC inhibitor that could help treat AD. Chemical synthesis and in vitro testing of diphenyl-imidazole analogs yielded a compound that inhibited human QC activity with an IC₅₀ of 1.23 µM. In HEK cells overexpressing QC and β amyloid, the compound decreased levels of the QC activity marker pyroglutamate-modified β amyloid compared with no treatment. In a mouse model of AD, the compound decreased AD-associated behaviors and levels of pyroglutamate-modified β amyloid and pyroglutamate-modified β amyloid plaques in the brain. Next steps include developing and testing additional QC inhibitors in models of AD and neuroinflammation...