Enantiomers of cysteine-modified SeNPs (d/lSeNPs) as inhibitors of metal-induced Aβ aggregation in Alzheimer's disease

Abstract

Chiral molecules, which selectively target and inhibit amyloid β-peptide (Aβ) aggregation, have potential use as therapeutic agents for the treatment of Alzheimer's disease (AD). Here we use cysteine enantiomer-modified SeNPs (abbreviated as D/LSeNPs) to demonstrate that surface chirality strongly influences the formation of Aβ aggregates in the presence of metal ions, such as Zn²⁺ or Cu²⁺. The two chiral molecule modified nanoparticles could inhibit the formation of Aβ fibrils by binding Aβ, thus blocking the formation of Aβ fibrils and blocking the metal binding sites. Of the two enantiomers, D/SeNPs appear to more effectively inhibit Aβ fibril formation due to a greater affinity for Aβ than that of L/SeNPs. Additionally, D/LSeNPs appeared to reduce Aβ and metal ion-induced neurotoxicity. Treatment with D/LSeNPs can also decrease the levels of intracellular reactive oxygen species, and stabilize the mitochondrial membrane potential. Of the two enantiomers, D/SeNPs were more effective in protecting the cells than L/SeNPs, and this could be due to D/SeNPs being selectively absorbed by PC12 cells, maintaining cellular redox potentials, and protecting cells against oxidative stress to a greater extent than L/SeNPs. From these results, it appears that chiral molecules can bring novel insight into better drug treatment designs for Alzheimer's disease.