Design Of Carboxylated Single-Walled Carbon Nanotubes As Highly Efficient Inhibitors Against A Beta 40 Fibrillation Based On The Hyber Mechanism

Misfolding and the subsequent self-assembly of amyloid-beta protein (A beta) is very important in the occurrence of Alzheimer's disease (AD). Thus, inhibition of A beta aggregation is currently an effective method to alleviate and treat AD. Herein, a carboxylated single-walled carbon nanotube (SWCNT-COOH) was rationally designed based on the hydrophobic binding-electrostatic repulsion (HyBER) mechanism. The inhibitory effect of SWCNT-COOH on A beta fibrillogenesis was first studied. Based on the results of thioflavin T fluorescence and atomic force microscopy imaging assays, it was shown that SWCNT-COOH can not only effectively inhibit A beta aggregation, but also depolymerize the mature fibrils of A beta. In addition, its inhibitory action will be affected by the content of carboxyl groups. Moreover, the influence of SWCNT-COOH on cytotoxicity induced by A beta was investigated by the MTT method. It was found that SWCNT-COOH can produce an anti-A beta neuroprotective effect in vitro. Molecular dynamics simulations showed that SWCNT-COOH significantly destroyed the overall and internal structural stability of an A beta 40 trimer. Moreover, SWCNT-COOH interacted strongly with the N-terminal region, turn region and C-terminal region of the A beta 40 trimer via hydrogen bonds, salt bridges and pi-pi interactions, which triggered a large structural disturbance of the A beta 40 trimer, reduced the beta-sheet content of the A beta 40 trimer and led to more disorder in these regions. All the above data not only reveal the suppressive effect of SWCNT-COOH on A beta aggregation, but also reveal its inhibitory mechanism, which provides a useful clue to exploit anti-A beta drugs in the future.