Effects of Carbon Nanoparticles on the Aggregation of Alzheimers Beta-Amyloid Peptide

Abstract

Amyloid deposits are implicated in the pathogenesis of many neurodegenerative diseases such asAlzheimer's disease (AD). The inhibition of β-sheet formation has been considered as the primary therapeutic strategy for the AD. In this presentation, I will present our recent results of the influences of different carbon nanoparticles (CNPs) (including graphene oxides, pristine single-walled carbon nanotubes--SWCNTs, hydroxylated SWCNTs, fullerenes including C60 and C180) on the aggregation of Aβ(16-22) and full-length Aβ peptides. Our replica exchange molecular dynamics (REMD) simulations show that CNPs shift the conformations of Aβ oligomers from ordered β-sheet-rich structures toward disordered coil aggregates. Atomic force microscopy (AFM) experiments further confirm the inhibitory effect of CNPs on Aβ fibrillation, in support of our REMD simulations. An important finding from our REMD simulations is that fullerene C180, albeit with the same number of carbon atoms as three C60 molecules (3C60) and smaller surface area than 3C60, displays an unexpected stronger inhibitory effect on the β-sheet formation. A detailed analysis of the CNP-peptide interaction reveals that strong inhibition of β-sheet formation by CNPs results from the strong hydrophobic and aromatic-stacking interactions between CNPs and Aβ peptides. These results demonstrate that CNPs can efficiently inhibit the aggregation of Aβ peptides and reveal the molecular insights into the inhibition mechanisms. Our study reveals the significant inhibitory role of fullerene hexagonal rings on the aggregation of Aβ(16-22) and full-length Aβ peptides and also provides novel insight into the development of drug candidates against Alzheimer's disease.