Proteasome activity regulated by charged gold nanoclusters: Implications for neurodegenerative diseases

Abstract

The 20S proteasome, the catalytic core particle of 26S proteasome, degrades a wide range of intracellular proteins, which is essential for many cellular processes. Herein, we have found that the 20S proteasome activity is either up- or down-regulated by introducing gold nanoclusters (AuNCs) coated with nine peptide tails in two different forms, AuNC(−) and AuNC(+), each encoding five consecutive negatively or positively charged amino acids. Molecular dynamics simulations reveal that AuNC(−) and AuNC(+) bind to different surfaces of the 20S proteasome, and respectively facilitate or hinder the opening of the central gate of 20S proteasome for substrate access to the internal active site for protein degradation. Furthermore, the addition of AuNC(-) induces protective effects in a cell model of Parkinson's disease, by up-regulating the proteasome activity under the condition of reduced ATP production, and enhancing the degradation of overexpressed α-synuclein, thereby attenuating the loss of cell viability. Our findings suggest the potential application of gold nanoclusters for treating neurodegenerative diseases.