Aggregation of amyloid-β (Aβ) peptides into prefibrillar
toxic oligomers is responsible for Alzheimer’s disease, which
is one of the most commonly known forms of neurodegenerative diseases.
It has been reported that the low-molecular weight Aβ(1–42)
trimer and its higher order oligomers are responsible for the cytotoxicity
in the neuronal cells, leading to their death. Various experimental
studies have shown that boron nitride nanotube (BNNTs) are noncytotoxic
for health and environment and biocompatible in living cells and can
be used as delivery vehicles for brain anticancer drugs. Here, we
investigate the effects of BNNT on the secondary structure of Aβ(1–42)
in the amyloid oligomerization process. We have performed long atomistic
molecular dynamics simulations of 4.0 μs in total to study the
structural stability of Aβ(1–42) trimer both in presence
and absence of BNNT in explicit solvent. It is found that in the absence
of BNNT, Aβ(1–42) trimer aggregates, leading to α-helix
to β-sheet transition, whereas BNNT provides structural stability
to the peptides by keeping them separated and preserving the initial
monomeric helical conformation of the Aβ(1–42) trimer.
It is found through a free-energy decomposition analysis that the
key residues (Lys28, Ile31, Ile32, Leu34, Val40, and Ile41) from the
C-terminal that are more responsible for β-sheet fibril formation
bind with the BNNT surface and block their structural conversion.
Due to the presence of polar B–N bonds, BNNT is less hydrophobic
as compared with the carbonaceous nanomaterials where large hydrophobicity
of these carbonaceous nanomaterials mostly destabilizes the secondary
structure of peptides. The current study reveals that the less hydrophobicity
of BNNT provides stability of the initial secondary structure of the
Aβ(1–42) trimer and hinders their aggregation. Hence,
the secondary structure stabilization in presence of BNNT provides
new possibilities for the design of different nanoparticles as therapeutic
agents for different types of amyloidogenesis by tuning their hydrophobicity.