PE859, A Novel Curcumin Derivative, Inhibits Amyloid-β and Tau Aggregation, and Ameliorates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8

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