Misfolding
and self-assembly of several intrinsically disordered
proteins into ordered β-sheet-rich amyloid aggregates emerged
as hallmarks of several neurodegenerative disorders such as Alzheimer’s
and Parkinson’s diseases. Here we show how the naringenin-embedded
nanostructure effectively retards aggregation and fibril formation
of α-synuclein, which is strongly associated with the pathology
of Parkinson’s-like diseases. Naringenin is a polyphenolic
compound from a plant source, and in our current investigation, we
reported the one-pot synthesis of naringenin-coated spherical and
monophasic gold nanoparticles (NAR-AuNPs) under optimized conditions.
The average hydrodynamic diameter of the produced nanoparticle was
∼24 nm and showed a distinct absorption band at 533 nm. The
zeta potential of the nanocomposite was ∼−22 mV and
indicated the presence of naringenin on the surface of nanoparticles.
Core-level XPS spectrum analysis showed prominent peaks at 84.02 and
87.68 eV, suggesting the zero oxidation state of metal in the nanostructure.
Additionally, the peaks at 86.14 and 89.76 eV were due to the Au–O
bond, induced by the hydroxyl groups of the naringenin molecule. The
FT-IR analysis further confirmed strong interactions of the molecule
with the gold nanosurface via the phenolic oxygen group. The composite
surface was found to interact with monomeric α-synuclein and
caused a red shift in the nanoparticle absorption band by ∼5
nm. The binding affinity of the composite nanostructure toward α-synuclein
was in the micromolar range (K
a∼
5.02 × 106 M–1) and may produce
a protein corona over the gold nanosurface. A circular dichroism study
showed that the nanocomposite can arrest the conformational fluctuation
of the protein and hindered its transformation into a compact cross-β-sheet
conformation, a prerequisite for amyloid fibril formation. Furthermore,
it was found that naringenin and its nanocomplex did not perturb the
viability of neuronal cells. It thus appeared that engineering of
the nanosurface with naringenin could be an alternative strategy in
developing treatment approaches for Parkinson’s and other diseases
linked to protein conformation.