… And Designed Ligands Target Metal-Amyloid-β Species

Newly designed small molecules could help probe the role of metals in the formation and neurotoxicity of amyloid-β protein aggregates associated with Alzheimer’s disease, chemists at the University of Michigan report (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1006091107). Metal ions are known to accumulate in the brains of individuals afflicted with Alzheimer’s, but the role of the metal ions is poorly understood. Mi Hee Lim and coworkers designed bifunctional diamines (one shown above) that target metal-containing amyloid-β species. These diamines feature a metal-binding site that chelates copper and zinc ions, as well as a framework that interacts with amyloid-β. During in vitro assays, the molecules modulated aggregation of amyloid-β by inhibiting formation of aggregates and promoting disassembly of already-formed aggregates. The molecules interacted similarly with amyloid-β aggregates in samples from the brains of Alzheimer’s patients. Such bifunctional compounds could be used as chemical tools to explore the biology of Alzheimer’s disease and as a starting point for potential therapeutics, the researchers note.