CLVFFA-Functionalized Gold Nanoclusters Inhibit Aβ40 Fibrillation, Fibrils' Prolongation, and Mature Fibrils' Disaggregation.

The abnormal aggregation of amyloid beta (Aβ or A beta) from monomeric proteins into amyloid fibrils is an important pathological contact to Alzheimer's disease (AD). Amyloid beta 40 (Aβ40), the pivotal biomarker of AD, aggregates to form amyloid plaques. For this reason, inhibition of amyloid fibrillation had become a crucial prevention and therapeutic strategy. Usually, LVFFA is the central hydrophobic fragment of Aβ and can inhibit the aggregation of Aβ40. In this work, in order to improve the inhibitory ability of LVFFA, hexapeptide CLVFFA were conjugated at the surface of Au clusters (AuNCs) to manufacture a nanosized inhibitor, AuNCs-CLVFFA. Thioflavin T fluorescence and transmission electron microscope results showed that AuNCs-CLVFFA inhibited Aβ40 fibrillogenesis, fibrils' prolongation, and mature fibrils' disaggregation. Furthermore, AuNCs as the backbone of the inhibitor showed extraordinary inhibition ability for Aβ40 aggregation at a low AuNCs-CLVFFA concentration. Free hexapeptide CLVFFA, at the same concentration, showed almost no inhibition. Additionally, the inhibitor could maintain the optical properties of nanoclusters, and the cell viability demonstrated that the inhibitor had good biocompatibility and may potentially be applied into AD therapy or treatment.