Modulation of β-amyloid aggregation by graphene quantum dots.

Changliang Liu,Yanlian Yang,Chen Wang,Lilusi Ma,Xiaocui Fang,Huan Huang

doi:10.1098/rsos.190271

Abstract

Misfolding and abnormal aggregation of β-amyloid peptide is associated with the onset and progress of Alzheimer's disease (AD). Therefore, modulating β-amyloid aggregation is critical for the treatment of AD. Herein, we studied the regulatory effects and mechanism of graphene quantum dots (GQDs) on 1–42 β-amyloid (Aβ1–42) aggregation. GQDs displayed significant regulatory effects on the aggregation of Aβ1–42 peptide as detected by thioflavin T (ThT) assay. Then, the changes of confirmations and structures induced by GQDs on the Aβ1–42 aggregation were monitored by circular dichroism (CD), dynamic light scattering (DLS) and transmission electron microscope (TEM). The in vitro cytotoxicity experiments further demonstrated the feasibility of GQDs on the regulation of Aβ1–42 aggregation. Meanwhile, the structural changes of a Aβ1–42/GQDs mixture in different pH revealed that electrostatic interaction was the major driving force in the co-assembly process of Aβ1–42 and GQDs. The proposed mechanism of the regulatory effects of GQDs on the Aβ1–42 aggregation was also deduced reasonably. This work not only demonstrated the potential feasibility of GQDs as therapeutic drug for AD but also clarified the regulatory mechanism of GQDs on the Aβ1–42 aggregation.

Highlights

Misfolding and abnormal aggregation of amyloid peptides or proteins is associated with a large number of diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, type II diabetes, mad cow disease and some types of cancers [1,2,3]
The graphene oxide (GO) was further oxidized to graphene quantum dots (GQDs) in the presence of concentrated H2SO4 and HNO3
The prepared GQDs exhibited a sheet-like structure and monodisperse in aqueous according to the transmission electron microscope (TEM) images

Summary

Introduction

Misfolding and abnormal aggregation of amyloid peptides or proteins is associated with a large number of diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, type II diabetes, mad cow disease and some types of cancers [1,2,3]. The cerebral extracellular amyloid plaques [4,5]. The amyloid plaques are considered to be formed by the 2 aggregation of b-amyloid peptide, which is an amphipathic polypeptide composed of 40 –42 amino acids in humans [6]. Ab1– 42 is the major variant in cerebrospinal fluid (CSF), and its aggregation is the main component of the amyloid plaques. Ab1– 42 peptide is considered as a major diagnostic biomarker and therapeutic target in the diagnosis and therapy of AD

Methods

Results

Conclusion