Abstract. Aggregation of amyloid- (A) and tau plays a crucial role in the onset and progression of Alzheimer's disease (AD). Therefore, the inhibition of A and tau aggregation may represent a potential therapeutic target for AD. Herein, we designed and synthesized both A 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 A aggregation in vitro and the therapeutic effects of PE859 on cognitive dysfunction via dual inhibition of A and tau aggregation in vivo. PE859 inhibited A aggregation in vitro and protected cultured cells from A-induced cytotoxicity. Furthermore, PE859 ameliorated cognitive dysfunction and reduced the amount of aggregated A and tau in brains of senescence-accelerated mouse prone 8 (SAMP8). These results warrant consideration of PE859 as a candidate drug for AD.
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