Two-dimensional materials can inhibit Aβ fibrillation in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a major life-limiting neurodegenerative disorder caused by extracellular aggregation of amyloid β (Aβ) peptides. This forms amyloid plaques in the brain resulting in dementia and even causing death. In spite of great efforts towards developing therapies to cure AD, unfortunately, treatment is often ineffective. Herein, we investigate the possibility of state-of-the-art two-dimensional (2D) nanomaterials to treat AD by evaluating their potential to perturb and disrupt Aβ peptide aggregates. The adsorption mechanism for a pre-formed Aβ fibril is carefully studied on five 2D materials, namely graphene, hexagonal boron nitride (h-BN), h2D-C₂N, g-C₃N₃, and g-C₃N₄. They are screened for their disrupting effects on the peptide aggregate. It is found that disruption of the Aβ fibril is directly related to the strength of its adsorption on the 2D material, which in turn, is dominated by the van der Waals interactions. h-BN shows a profound disruption of the Aβ fibril followed by graphene. The nitrogen-containing carbon-based 2D materials, h2D-C₂N, g-C₃N₃, and g-C₃N₄, are found to be rather poor in this aspect. Structural disruption parameter ρ_d is proposed as an index to rank the potency of 2D materials to inhibit Aβ fibrillation. h-BN and graphene are shown to be highly potent towards disruption of misfolded protein aggregates like Aβ fibrils.