Anti-amyloidogenic effects of soybean isoflavones in vitro: Fluorescence spectroscopy demonstrating direct binding to Aβ monomers, oligomers and fibrils

Biochimica Et Biophysica Acta
Mie HirohataMasahito Yamada

Abstract

Alzheimer's disease is characterized by the presence of extracellular deposits of amyloid, primarily composed of the amyloid β-protein (Aβ). A growing body of evidence indicates that oligomeric forms of Aβ play a critical role in disease causation. Soybean isoflavones are flavonoids with an isoflavone backbone. Isoflavones have been reported to protect against Aβ-induced neurotoxicity in cultured cell systems, the molecular mechanisms remain unclear. Our previous studies demonstrated that red wine-related flavonoids with a flavone backbone are able to inhibit Aβ assembly and destabilize preformed Aβ aggregates. Here, we show that isoflavones, especially glycitein and genistein, have anti-fibrillization, anti-oligomerization and fibril-destabilizing effects on Aβ(1-40) and Aβ(1-42)in vitro at physiological pH and temperature, by using nucleation-dependent polymerization monitored by thioflavin T fluorescence, atomic force microscopy, electron microscopy, and photo-induced cross-linking of unmodified proteins followed by SDS-PAGE. Our three-dimensional fluorescence spectroscopic analyses demonstrated that glycitein interacted with Aβ monomers, oligomers and fibrils, indicating specific binding of glycitein to these Aβ species. Gl...Continue Reading

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Citations

Oct 9, 2013·Cellular and Molecular Neurobiology·Norsharina IsmailKim Wei Chan
Jan 26, 2013·Journal of Peptide Science : an Official Publication of the European Peptide Society·Wei ZhangJianting Miao
Nov 14, 2017·PloS One·Mohsen MahdavimehrMohsen Nemat-Gorgani
Oct 16, 2015·The Journal of Biological Chemistry·Paola FlorioRodolfo Berni
Oct 30, 2020·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Akira SekikawaChendi Cui
Mar 12, 2021·Brain and Behavior·Xiaoying DuanHong Ding
Oct 6, 2021·British Journal of Pharmacology·Seong Soo A AnSun Yeou Kim

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