Novel curcumin derivatives as potent inhibitors of amyloid ? aggregation.

ABSTRACT: Modulation of abnormal amyloid ? (A?) aggregation is considered to be a potential therapeutic target for Alzheimer's disease (AD). Recent in vitro and in vivo experiments suggest that inhibition of A? aggregation by curcumin would exert favorable effects for preventing or treating AD. We have previously synthesized a series of novel curcumin derivatives. In this study, we investigated the effects of our curcumin derivatives on A? aggregation and the cell toxicities of A? aggregates. According to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) profiles, 14 of 41 compounds showed a significant increase in the densities of the bands of A? (1-42) by incubation during the aggregation process relative to those of A? (1-42) prepared in the presence of the vehicle control. Of the 14 compounds, four compounds additionally reduced cell toxicity of the A? aggregates by incubation during the aggregation process. A significant positive correlation was observed between the cell viability and densities of the bands at ranges of 15-20, 20-37, 37-75, and 75-200 kDa in SDS-PAGE. On the basis of these results, we propose four curcumin derivatives with potential for preventing AD. These curcumin derivatives exhibited high inhibitory effects on A? aggregation and induced the formation of lower molecular size A? species that have weaker cell toxicity. These compounds may exert therapeutic effects on AD in future in vivo studies.

SUBMITTER: Yanagisawa D 

PROVIDER: S-EPMC5669405 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other