Naringenin-Functionalized Gold Nanoparticles and Their Role in α-Synuclein Stabilization

Abstract

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.

Mechanism of the interaction of toxic SOD1 fibrils with two potent polyphenols: curcumin and quercetin

“…Earlier, many researchers have monitored the effects of polyphenols, specifically quercetin and curcumin, on the disaggregation of amyloid fibrils of Aβ, τ and α-synuclein using experimental and computational methods. 21,57–66 Quercetin was found to destabilize the pre-formed oligomers of Aβ peptide 33 and α-synuclein. 60,63 Curcumin was also effective in disintegrating the fibrils of Aβ, 58 τ peptide, 31 and α-synuclein.…”

Investigation of Drug Release Behavior of Cyclomatrix Polyphosphazene Microparticles Decorated with Gold and Silver Nanoparticles

“…In addition, the absence of any peak at a bond energy value of about 92 eV in the spectrum supports that all of the Au 3 + ions adsorbed by p(CTP-co-MMCA) microparticles were successfully reduced to Au 0 by TA. [33] As seen from the data obtained from XPS analysis, the p(CTP-co-MMCA)@Au composite structure was successfully synthesized and the oxidation state of the entire gold component in the structure is Au 0 .…”

Tau- and α-synuclein-targeted gold nanoparticles: applications, opportunities, and future outlooks in the diagnosis and therapy of neurodegenerative diseases

“…9 d–f). Another recent study was carried out by Maity et al [ 243 ] using GNS functionalized with naringenin, a polyphenolic compound obtained mainly from several citrus fruits, showing an inhibitory effect on α-syn kinetics and stabilizing α-syn in its helix-α structure [ 219 ]. Similar results were observed using GNS functionalized with β-boswellic acid, a plant-derived terpenoid, which inhibit the Tau aggregation process [ 244 ].…”