Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-beta C-terminal peptides

摘要

Amyloid-beta (A beta) deposition and oxidative stress observed in the brains of patients with Alzheimer's disease (AD) are important targets for therapeutic intervention. In this study, we conjugated the antioxidants caffeic acid (CA) and dihydrocaffeic acid (DHCA) to A beta(1-42) C-terminal motifs (A beta(x-42): x = 38, 40) to synthesize CA-A beta(x-42) and DHCA-A beta(x-42), respectively. Among the compounds, CA-A beta(38-42) exhibited potent inhibitory activity against A beta(1-42) aggregation and scavenged A beta(1-42)-induced intracellular oxidative stress. Moreover, CA-A beta(38-42) significantly protected human neuroblastoma SH-SY5Y cells against A beta(1-42)-induced cytotoxicity, with an IC50 of 4 mu M. These results suggest that CA-A beta(38-42) might be a potential lead for the treatment of AD. (C) 2016 Elsevier Ltd. All rights reserved.