Amyloid-β (Aβ) peptides spontaneously aggregate into β- and cross-β-sheets in model brain membranes. These nanometer sized can fuse into larger micrometer sized clusters and become extracellular and serve as nuclei for further plaque and fibril growth. Curcumin and homotaurine represent two different types of Aβ aggregation inhibitors. While homotaurine is a peptic antiaggregant that binds to amyloid peptides, curcumin is a nonpeptic molecule that can inhibit aggregation by changing membrane properties. By using optical and fluorescent microscopy, X-ray diffraction, and UV-vis spectroscopy, we study the effect of curcumin and homotaurine on Aβ25-35 aggregates in synthetic brain membranes. Both molecules partition spontaneously and uniformly in membranes and do not lead to observable membrane defects or disruption in our experiments. Both curcumin and homotaurine were found to significantly reduce the number of small, nanoscopic Aβ aggregates and the corresponding β- and cross-β-sheet signals. While a number of research projects focus on potential drug candidates that target Aβ peptides directly, membrane-lipid therapy explores membrane-mediated pathways to suppress peptide aggregation. Based on the results obtained, we conclude that membrane active drugs can be as efficient as peptide targeting drugs in inhibiting amyloid aggregation in vitro.
Keywords: Alzheimer’s disease; Amyloid-β aggregation; aggregation inhibitor; cross-β-sheets; curcumin; homotaurine.