Sidra Islam, Michael Do, Brett S Frank, Grant L Hom, Samuel Wheeler, Hisashi Fujioka, Benlian Wang, Geeta Minocha, David R Sell, Xingjun Fan, Kirsten J Lampi, Vincent M Monnier
Gamma crystallins play a major role in age-related lens transparency. Their destabilization by mutations and physical chemical insults is strongly associated with cataract formation. Therefore, drugs that increase their stability should have anti-cataract properties. To this end, here we screened 2,560 FDA-approved drugs and natural compounds for their ability to suppress or worsen H2 O2 and/or heat-mediated aggregation of bovine γ-crystallins. The top two drugs, Closantel (C), an anti-helmintic drug, and Gambogic Acid (G), a xanthonoid, attenuated thermal-induced protein unfolding as determined by fluorescence spectroscopy, aggregation as shown by turbidimetry, dynamic light scattering, and electron microscopy of human or mouse recombinant crystallins...
August 26, 2022: Journal of Biological Chemistry