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

作者：Hirohata Mie; Ono Kenjiro; Takasaki Jun ichi; Takahashi Ryoichi; Ikeda Tokuhei; Morinaga Akiyoshi; Yamada Masahito^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2012, 1822(8): 1316-1324.

DOI：10.1016/j.bbadis.2012.05.006

• Alzheimer%26apos
• s disease
• Amyloid beta-protein oligomer
• Fragment
• Photo-induced cross-linking of unmodified proteins (PICUP)
• Glycitein
• Three-dimensional fluorescence spectroscopy

Alzheimer%26apos;s disease is characterized by the presence of extracellular deposits of amyloid, primarily composed of the amyloid beta-protein (A beta). A growing body of evidence indicates that oligomeric forms of A beta play a critical role in disease causation. Soybean isoflavones are flavonoids with an isoflavone backbone. Isoflavones have been reported to protect against A beta-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 A beta assembly and destabilize preformed A beta aggregates. Here, we show that isoflavones, especially glycitein and genistein, have anti-fibrillization, anti-oligomerization and fibril-destabilizing effects on A beta(1-40) and A beta(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 A beta monomers, oligomers and fibrils, indicating specific binding of glycitein to these A beta species. Glycitein also interacted with different A beta fragments (A beta(1-42), A beta(1-40), A beta(1-16) and A beta(25-35)), exhibiting the highest fluorescence enhancement with A beta(25-35). We speculated that glycitein%26apos;s anti-amyloidogenic properties are specifically mediated by its binding to A beta monomers, oligomers and fibrils. Isoflavones may hold promise as a treatment option for preventative strategies targeting amyloid formation in Alzheimer%26apos;s disease.

• 出版日期2012-8