Nickel oxide nanoparticles increase α-synuclein amyloid formation and relevant overexpression of inflammatory mediators in microglia as a marker of Parkinson's disease

The study of protein aggregation has received increasing attention owing to their potential role development of neuroadaptive disease. Elsewhere, the use of nanoparticles (NPs) including nickel oxide (NiO) in medicine can result in the interaction of NPs with proteins and exert a toxic effect. Thus, this study was aimed to examine the effects of synthesized NiO NPs via thermal decomposition method on the structural and kinetic characteristics of a-synuclein-protein fibrillization through thioflavin T (ThT) fluorescence, Transmission electron microcopy (TEM), Congo red adsorption, and far-UV circular dichroism (CD) analysis. Also, the increased cytotoxicity of alpha-synuclein amyloids formed in the presence of NiO NPs was explored by evaluation of oxidative stress and expression of inflammatory and apoptotic mediators in microglia cells as determined by reactive oxygen species (ROS), superoxide dismutase (SOD) and catalase (CAT) activities, and quantitative real-time PCR (qRT-PCR) assays. The obtained results indicated that the fabricated NiO NPs with a dominant average size of about 50 nm led to the secondary structural changes of alpha-synuclein and accelerated the protein amyloid formation through a significant increase in the k(b) and k(a) parameters as the homogeneous nucleation rate constant and the secondary rate constant, respectively. Also, it was shown that alpha-synuclein amyloid aged in the presence of NiO NPs significantly enhanced alpha-synuclein amyloid-induced cytotoxicity through production of high level of ROS, deactivation of SOD and CAT, overexpression of inflammatory [tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), interleukin-1 beta (IL-1 beta)] and apoptotic [B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and caspase-3) genes over that of alpha-synuclein amyloid alone in EOC 13.31 mouse microglia cell line. The present work indicated, for the first time, the acceleration effect of NiO NPs against alpha-synuclein amyloid fibrillization and associated neurotoxicity as a marker of Parkinson's disease. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

This study investigated the effects of NiO NPs on protein aggregation and found that NiO NPs accelerated the formation of α-synuclein amyloids and enhanced their cytotoxicity. Through a series of analyses, the results showed that the interaction between NiO NPs and α-synuclein exacerbated the development of neuroadaptive diseases.