Hydrophobic interaction of glycitein and α-synuclein inhibits the protein aggregation: A future perspective for modulation of Parkinson's disease.

Despite the worldwide prevalence of Parkinson's disease (PD), there are currently no effective methods for treating or preventing α-synucleinopathy. Research has demonstrated that small molecules are capable of preventing α-synuclein aggregation and the associated neurotoxicity. Nonetheless, the specific anti-amyloid mechanism of these compounds is not thoroughly comprehended in detail. In this study, the interaction between glycitein and α-synuclein was evaluated. Furthermore, the aggregation of α-synuclein in the presence of glycitein was examined utilizing several arrays. Thermodynamic results indicated that glycitein, an O-methylated isoflavone, binds to α-synuclein by creating a static complex, wherein non-covalent interactions, especially hydrophobic forces, served as the primary intermolecular forces stabilizing the complex. We further found that glycitein serves as a promising bioactive agent against α-synuclein amyloid fibrillation in a concentration-dependent fashion, modulating the formation of hydrophobic regions, the solution's surface tension, and the shift from natural random coil to β-sheet configurations, in addition to potential interactions with α-synuclein monomers and amyloid fibril formations. Moreover, we noted that glycitein prevents the neurotoxicity caused by α-synuclein aggregates by shielding PC12 cells from ROS production and caspase-3 activation. These results emphasize the significance of using bioactive small compounds for the prevention and treatment of PD.