Aggregation of amyloid-â (Aâ) and tau plays a crucial role in the onset and progression of Alzheimer's disease (AD). Therefore, the inhibition of Aâ and tau aggregation may represent a potential therapeutic target for AD. Herein, we designed and synthesized both Aâ and tau dual aggregation inhibitors based on the structure of curcumin and developed the novel curcumin derivative PE859. In this study, we investigated the inhibitory activity of PE859 on Aâ aggregationin vitro and the therapeutic effects of PE859 on cognitive dysfunction via dual inhibition of Aâ and tau aggregation in vivo. PE859 inhibited Aâ aggregation in vitro and protected cultured cells from Aâ-induced cytotoxicity. Furthermore, PE859 ameliorated cognitive dysfunction and reduced the amount of aggregated Aâ and tau in brains of senescence-accelerated mouse prone 8 (SAMP8). These results warrant consideration of PE859 as a candidate drug for AD.
Aging Amyloid beta-Peptides