Inhibition of Alzheimer's Aβ1-42 Fibrillogenesis and Removal of Copper Ions by Polypeptides Modified Gold Nanoparticles.

Abstract

Aggregation and fibrillation of β-amyloid peptides (Aβ) as well as accumulation of toxic metal ions have been believed to be the central events to cause Alzheimer's disease (AD). Thus, an attractive therapeutic tactic for AD is to design and synthesize inhibitors and metal chelators to prevent Aβ aggregation and chelate toxic metal ions. In this study, the polypeptide functionalized gold nanoparticles (PFGNP) were obtained by modifying polypeptides Cys-Gly-Gly-Gly-Leu-Pro-Phe-Phe-Asp (CGGGLPFFD) and Cys-Gly-Gly-Gly-Gly-Gly-His (CGGGGGH) onto gold nanoparticles through gold-sulfur bond. The inhibitory properties of PFGNP toward Aβ1-42 fibril formation was assessed by thioflavin T (ThT) fluorescence method and corroborated by atomic force microscopy analysis. The ability of PFGNP to complex copper ions was studied by electrochemical method. The experimental results reveal that PFGNP can effectively chelate copper ions and significantly inhibit the fibrillation of Aβ1-42 . Moreover, PFGNP exhibits significantly protective effect on Aβ-induced cytotoxicity toward human neuroblastoma SH-SY5Y cells.