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

Abstract 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 α-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 α-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 α-synuclein and accelerated the protein amyloid formation through a significant increase in the kb and ka parameters as the homogeneous nucleation rate constant and the secondary rate constant, respectively. Also, it was shown that α-synuclein amyloid aged in the presence of NiO NPs significantly enhanced α-synuclein amyloid -induced cytotoxicity through production of high level of ROS, deactivation of SOD and CAT, overexpression of inflammatory [tumor necrosis factor-alpha (TNFα), interleukin-1 (IL-1), interleukin-1β (IL-1β)] and apoptotic [B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and caspase-3) genes over that of α-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 α-synuclein amyloid fibrillization and associated neurotoxicity as a marker of Parkinson's disease.