Cyanidin-3-O-glucoside inhibits Aβ40 fibrillogenesis, disintegrates preformed fibrils, and reduces amyloid cytotoxicity
Abstract
Alzheimer's disease (AD) is mainly caused by the fibrillogenesis of amyloid-β protein (Aβ). Therefore, the development of effective inhibitors against Aβ fibrillogenesis offers great hope for the treatment of AD. Cyanidin-3-O-glucoside (Cy-3G) is a commonly found anthocyanin that is mainly present in fruits, with established neuroprotective effects in situ. However, it remains unknown if Cy-3G can prevent Aβ fibrillogenesis and alleviate the corresponding cytotoxicity. In this study, extensive biochemical, biophysical, biological and computational experiments were combined to address this issue. It was found that Cy-3G significantly inhibits Aβ40 fibrillogenesis and disintegrates mature Aβ fibrils, and its inhibitory capacity is dependent on the Cy-3G concentration. The circular dichroism results showed that Cy-3G and Aβ40 at a molar ratio of 3 : 1 slightly prevents the structural transformation of Aβ40 from its initial random coil to the β-sheet-rich structure. Co-incubation of Aβ40 with Cy-3G significantly reduced the production of intracellular reactive oxygen species induced by Aβ40 fibrillogenesis and thus reduced Aβ40-induced cytotoxicity. Molecular dynamics simulations revealed that Cy-3G disrupted the β-sheet structure ...Continue Reading
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