Curcumin and Homotaurine Suppress Amyloid-β25–35 Aggregation in Synthetic Brain Membranes
- Xingyuan ZouXingyuan ZouDepartment of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, CanadaOrigins Institute, McMaster University, Hamilton, ON L8S 4L8, CanadaMore by Xingyuan Zou
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- Sebastian HimbertSebastian HimbertDepartment of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, CanadaOrigins Institute, McMaster University, Hamilton, ON L8S 4L8, CanadaMore by Sebastian Himbert
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- Alix DujardinAlix DujardinDepartment of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, CanadaOrigins Institute, McMaster University, Hamilton, ON L8S 4L8, CanadaDepartment of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4L8, CanadaMore by Alix Dujardin
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- Janos JuhaszJanos JuhaszDepartment of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, CanadaDepartment of Medical Physics, Juravinski Cancer Centre, Hamilton, ON L8V 5C2, CanadaMore by Janos Juhasz
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- Samantha RosSamantha RosDepartment of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4L8, CanadaMore by Samantha Ros
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- Harald D. H. StöverHarald D. H. StöverDepartment of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4L8, CanadaMore by Harald D. H. Stöver
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- Maikel C. Rheinstädter*Maikel C. Rheinstädter*Email: [email protected]Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, CanadaOrigins Institute, McMaster University, Hamilton, ON L8S 4L8, CanadaMore by Maikel C. Rheinstädter
Abstract
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.
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