Zinc Oxide Nanoparticle Interface Moderation Enhances the Extent of  Synuclein Sequestering Against the Protein Amyloidosis

Abstract

Parkinson’s disease is a progressive neurodegenerative disorder that is often associated with plaque deposition, which is known as Lewy Body. Lewy Bodies are predominantly composed of amyloid fibrils of α-synuclein protein. This protein is a soluble, intrinsically unstructured protein (IUP) with proposed multiple physiological functions. α-Synuclein has a basic amino acid-rich N-terminus, acidic amino acid-rich C-terminus, and aggregation-prone non-amyloid  component (NAC) middle region. The NAC region is highly prone to amyloid aggregation upon neutralization of either the N- or C terminus or both. α-Synuclein amyloid aggregation goes through cytotoxic intermediate(s) formation, leading to structurally mature cross-β sheet-rich fibrils, as an end product. Thus, sequestering monomeric IUP onto a biologically inert surface is likely to retard Parkinson’s onset or progression. Metal nanoparticles with biocompatible nature and for their tuneable physicochemical properties have been adopted in different biological applications. Thus, sequestering of α-synuclein monomer onto the metal nanoparticle surface will potentially impede Parkinson’s onset/progression. In this line, the positive surface potential zinc oxide nanoparticle (ZnONP) and the nanoparticle with moderated negative surface-functional group(s) having interaction with α-synuclein is explored, where the interaction studies indicate that the NAC region of α-synuclein mostly interacts with the nanoparticle interface to trigger the sequestering of the monomeric protein, inhibiting the protein aggregation. Furthermore, TEM micrographs of the protein-adsorbed ZnONP surface, shows mesh-like amorphous aggregates compared to fibril-like aggregates for incubated α-synuclein only samples. Interestingly, α synuclein-ZnONP complexes showed remarkably lowered cytotoxicity against the SH-SY5Y cell in vitro compared to α-synuclein fibrils only or the nanoparticle-only treatments. Henceforth, this study provides an alternative novel therapeutic approach to impede Parkinson’s disease onset and progression.