Zinc oxide nanoparticle interface moderation enhances the extent of α-synuclein sequestering against the protein...

Parkinson's disease is a progressive neurodegenerative disorder that is often associated with plaque deposition, known as Lewy Bodies. Lewy Bodies are predominantly composed of α-synuclein amyloid fibrils. α-Synuclein is a soluble intrinsically disordered protein (IDP) with proposed multiple physiological functions, consisting of aggregation-prone non-amyloid β component (NAC) region in its sequence. Amyloid aggregation of α-synuclein goes through a cytotoxic intermediate(s), leading to structurally mature cross-β sheet-rich fibrils as its end product. Metal nanoparticles with a biocompatible nature have been adopted for different biological applications. Thus, sequestering of α-synuclein monomer onto the metal nanoparticle will potentially impede Parkinson's onset/progression. In this study, interaction of α-synuclein with zinc oxide nanoparticle (ZnONP) having positive surface potential, and moderated ZnONP with negative surface-functional group(s), were explored. The interaction studies indicate that the NAC region interacts with the nanoparticle to sequester the monomeric protein into an amorphous aggregate, thus extending the lag phase of protein fibrillation. Interestingly, α-synuclein complexed with ZnONP exhibits remarkably lowered cytotoxicity against the SH-SY5Y cell in-vitro, compared to the treatment with only ZnONP interfaces or α-synuclein fibrils.