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

Abstract

Amyloid-β (Aβ) 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 Aβ1–42 C-terminal motifs (Aβx–42: x=38, 40) to synthesize CA-Aβx–42 and DHCA-Aβx–42, respectively. Among the compounds, CA-Aβ38–42 exhibited potent inhibitory activity against Aβ1–42 aggregation and scavenged Aβ1–42-induced intracellular oxidative stress. Moreover, CA-Aβ38–42 significantly protected human neuroblastoma SH-SY5Y cells against Aβ1–42-induced cytotoxicity, with an IC50 of 4μM. These results suggest that CA-Aβ38–42 might be a potential lead for the treatment of AD.