%0 Journal Article
%T Hydroxylated Single-Walled Carbon Nanotubes Inhibit A¦Â42 Fibrillogenesis, Disaggregate Mature Fibrils, and Protect against A¦Â42-Induced Cytotoxicity
%J -
%D 2019
%R https://doi.org/10.1021/acschemneuro.8b00441
%X The fibrillogenesis of amyloid-¦Â protein (A¦Â) is considered a crucial factor in the pathogenesis of Alzheimer¡¯s disease (AD). Hence, inhibiting A¦Â fibrillogenesis is regarded as the primary therapeutic strategy for the prevention and treatment of AD. However, the development of effective inhibitors against A¦Â fibrillogenesis has faced significant challenges. Previous studies have shown that pristine single-walled carbon nanotubes (SWNTs) can inhibit fibrillogenesis of some amyloid proteins. However, the poor dispersibility of SWNTs in an aqueous environment greatly hinders their inhibitory efficacy. Here, we examined the inhibitory activity of hydroxylated SWNTs (SWNT-OH) on the aggregation and cytotoxicity of A¦Â42 using thioflavin T (ThT) fluorescence, atomic force microscopy (AFM), cellular viability assays, and molecular dynamics (MD) simulations. ThT and AFM results showed that SWNT-OH inhibits A¦Â42 fibrillogenesis and disaggregates preformed amyloid fibrils in a dose-dependent manner. Furthermore, the ratio of hydroxyl groups in SWNT-OH is crucial for their effect against A¦Â42 aggregation. SWNT-OH exerted cytoprotective effects against A¦Â42 fibrillation-induced cytotoxicity. The results of free-energy decomposition studies based on MD simulations revealed that nonpolar interactions, and especially van der Waals forces, contributed most of the free energy of binding in the SWNT-OH¨CA¦Â complex. Two regions of the A¦Â pentamer were identified to interact with SWNT-OH, spanning H13¨CQ15 and V36¨CG38. The findings presented here will contribute to a comprehensive understanding of the inhibitory effect of hydroxylated nanoparticles against A¦Â fibrillogenesis, which is critical for the search for more effective agents that can counteract amyloid-mediated pathologies
%U https://pubs.acs.org/doi/10.1021/acschemneuro.8b00441