Interactions of the Aβ(1–42) Peptide with Boron Nitride Nanoparticles of Varying Curvature in an Aqueous Medium: Different Pathways to Inhibit β-Sheet Formation

Abstract

The aggregation of amyloid β (Aβ) peptide triggered by its conformational changes leads to the commonly known neurodegenerative disease of Alzheimer's. It is believed that the formation of β sheets of the peptide plays a key role in its aggregation and subsequent fibrillization. In the current study, we have investigated the interactions of the Aβ(1−42) peptide with boron nitride nanoparticles and the effects of the latter on conformational transitions of the peptide through a series of molecular dynamics simulations. In particular, the effects of curvature of the nanoparticle surface are studied by considering boron nitride nanotubes (BNNTs) of varying diameter and also a planar boron nitride nanosheet (BNNS). Altogether, the current study involves the generation and analysis of 9.5 μs of dynamical trajectories of peptide-BNNT/BNNS pairs in an aqueous medium. It is found that BN nanoparticles of different curvatures that are studied in the present work inhibit the conformational transition of the peptide to its β-sheet form. However, such an inhibition effect follows different pathways for BN nanoparticles of different curvatures. For the BNNT with the highest surface curvature, i.e., (3,3) BNNT, the nanoparticle is found to inhibit β-sheet formation by stabilizing the helical structure of the peptide, whereas for planar BNNS, the β-sheet formation is prevented by making more favorable pathways available for transitions of the peptide to conformations of random coils and turns. The BNNTs with intermediate curvatures are found to exhibit diverse pathways of their interactions with the peptide, but in all cases, essentially no formation of the β sheet is found whereas substantial β-sheet formation is observed for Aβ(1−42) in water in the absence of any nanoparticle. The current study shows that BN nanoparticles have the potential to act as effective tools to prevent amyloid formation from Aβ peptides.

The Role of Microbiome in Brain Development and Neurodegenerative Diseases

“…Sorout and colleagues discovered that BN nanoparticles of various curvatures hinder the peptide’s conformational transition to its β-sheet form, that plays a key role in the aggregation and subsequent fibrillization of amyloid. This inhibition of β-sheet formation is by stabilizing the helical structure of the peptide (BNNT with the highest surface curvature), by making more favorable pathways available for transitions of the peptide to conformations of random coils and turns (planar BNNS), showing that BN nanoparticles have the potential to act as effective tools to prevent amyloid formation from Aβ peptides [ 185 ]. Novel boron-based compounds (BBCs) have been produced and tested as prospective candidates for the development of new Alzheimer’s disease treatments (AD).…”

Advanced nanomaterials for modulating Alzheimer's related amyloid aggregation

“…Adsorption/size effect Delay [85] GO-ThS Photothermal Disaggregation [91] GOIO Adsorption Inhibition [84] GO@Dau Adsorption/anti-oxidation Inhibition/ Disaggregation [94] g-C 3 N 4 Chelation Inhibition/Disaggregation [108] g-C 3 N 4 @Pt Noncovalent interactions/ platinum coordination/ photooxygenation Inhibition/Disaggregation [105] Au/g-C 3 N 4 Photooxygenation Disaggregation [104] GO/g-C 3 N 4 Photooxygenation Disaggregation [106] g-C 3 N 4 Photooxygenation Inhibition [107] BP Adsorption Regulate the aggregation [118] PEG-LK7@BP Electrostatic/ hydrophobic interactions Inhibition [119] BP@BTA Photooxygenation Inhibition [126] MoS 2 Adsorption Modulation [137] MoS 2 -Co Photothermal Inhibition/Disaggregation [141] MoS 2 /AuNR Photothermal Modulation/Disaggregation [140] AuNPs [120] BNNS Adsorption Modulation [144] 3 Zero-dimensional nanomaterials Zero-dimensional (0D) nanomaterials, including gold nanoparticles (GNPs), gold nanoclusters, organic and inorganic quantum dots, metal oxide nanoparticles, and carbon-based nanomaterials, have attracted extensive research interest in the field of biomedicine in recent years. [149] The edge effect, quantum confinement effect, ultrasmall size and good biocompatibility of 0D nanomaterials endow their many functions and special performance, such as photoluminescence (PL), tissue penetration, bioactivity, and drug loading capability.…”

“…2D COFs, MXenes, hexagonal boron nitride and so on have also been reported for use in AD diagnosis and treatment. 120,143,144 Covalent organic frameworks (COFs) are a new generation of nanoparticles consisting of carbon, oxygen, nitrogen and hydrogen atoms with excellent biocompatibility. 145 2D COFs have a highly tunable structure and can be designed to cross the blood-brain barrier and inhibit Ab aggregation.…”

“…2D COFs, MXenes, hexagonal boron nitride and so on have also been reported for use in AD diagnosis and treatment. 120,143,144…”

Influence of Ion Specificity and Concentration on the Conformational Transition of Intrinsically Disordered Sheep Prion Peptide

“…[21] Recently, various techniques are adopted to manipulate the interfacial environments of IDPs to disintegrate the fibrillization process and inhibition of partially ordered misfolded states. Different nanomaterials made of polymer, gold nanoparticles/nanocluster, [22] boron nitride nanotubes/nanosheet, [23,24] small organic molecules, [25,26] and ionic liquids [27] are reported to burst the mature fibril already deposited in the brain or inhibit the prefibrillar aggregation of IDPs. The major limitation of the above-mentioned material is its efficiency to cross the bloodbrain barrier and interact with infected neuronal cells to disintegrate amyloid formation.…”