Anti-amyloidogenic effects of soybean isoflavones in vitro: Fluorescence spectroscopy demonstrating direct binding to Aß monomers, oligomers and fibrils.
Biochim Biophys Acta
; 1822(8): 1316-24, 2012 Aug.
Article
en En
| MEDLINE
| ID: mdl-22587837
Alzheimer's disease is characterized by the presence of extracellular deposits of amyloid, primarily composed of the amyloid ß-protein (Aß). A growing body of evidence indicates that oligomeric forms of Aß play a critical role in disease causation. Soybean isoflavones are flavonoids with an isoflavone backbone. Isoflavones have been reported to protect against Aß-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 Aß assembly and destabilize preformed Aß aggregates. Here, we show that isoflavones, especially glycitein and genistein, have anti-fibrillization, anti-oligomerization and fibril-destabilizing effects on Aß(1-40) and Aß(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 Aß monomers, oligomers and fibrils, indicating specific binding of glycitein to these Aß species. Glycitein also interacted with different Aß fragments (Aß(1-42), Aß(1-40), Aß(1-16) and Aß(25-35)), exhibiting the highest fluorescence enhancement with Aß(25-35). We speculated that glycitein's anti-amyloidogenic properties are specifically mediated by its binding to Aß monomers, oligomers and fibrils. Isoflavones may hold promise as a treatment option for preventative strategies targeting amyloid formation in Alzheimer's disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Péptidos beta-Amiloides
/
Isoflavonas
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Países Bajos