High efficiency and related mechanism of Au(RC) nanoclusters on disaggregating Aβ fibrils

Abstract

Revealing the disaggregating mechanism of amyloids fibrils under nanomaterials action is a key issue for their successful future use in therapy of neurodegenerative and overall amyloid-related diseases. Herein a gold nanocluster stabilized by Arg-Cys dipeptide (Au(RC)NCs) was synthesized to investigate its disaggregation activity toward Aβ fibrils by using Thioflavin-T (ThT) fluorescence assay and atomic force microscopy. It was demonstrated that Au(RC)NCs is very effective in disaggregating preformed Aβ fibrils, and characterized by the ultra-low apparent completely disaggregation concentration at the dose of 10 μg·mL−1. A possible disaggregation mechanism based on Au(RC)NCs triggering the disassembly of Aβ fibrils into a dynamic equilibrium was proposed. The introduction of Au(RC)NCs with appropriate dose (5 μg·mL−1) can trigger the disassemble process of mature Aβ fibrils into a critical state, at this very moment, if there is no more nano-disassembler, destruction of old Aβ fibrils and formation of new Aβ fibrils are thus in permanent dynamic equilibrium; in contrast, if there is more nano-disassembler (>10 μg·mL−1), the dynamic equilibrium prefer to shift to the direction of Aβ further disassembly. Moreover, Au(RC)NCs with dosage over 10 μg·mL−1 exhibited superb protection effect against Aβ-induced cytotoxicity in cell experiments. This study not only proposed a possible disassembly mechanism of amyloids fibrils under nanomaterials action, but also provide Au(RC)NCs as a promising high-effective nano-disassembler to disassemble unwanted amyloid aggregates.