Identification of novel Aβ inhibitors

Targeting amyloid-β (Aβ) aggregation and accumulation has been pursued as a major potential therapeutic strategy against AD, but no compound has yet gained regulatory approval. Habchi et al. now describe the use of a quasi-structure-based and kinetics-based drug discovery approach to identify a pool of ligands for retinoid acid receptors and retinoid X receptors that inhibit aggregation of the 42-residue form of Aβ (Aβ₄₂). The compounds inhibited Aβ₄₂ aggregation in human cerebrospinal fluid solutions and rescued Aβ₄₂-mediated dysfunction in a Caenorhabditis elegans model of Aβ₄₂-mediated cytotoxicity.