title: Nano Zinc Oxide Inhibits Fibrillar Growth and Suppresses Cellular Toxicity of Lysozyme Amyloid.
abstract: Deposition of amyloid fibers has been a common pathological event in many neurodegenerations, such as Alzheimer's disease, Parkinson's disease, and Prion disease. Although various therapeutic interventions have been reported, nanoparticles have recently been considered as possible inhibitors of amyloid fibrillation. Here, we reported the effect of three different forms of zinc oxide nanoparticles (ZnONP): uncapped (ZnONPuncap), starch-capped (ZnONPST), and self-assembled (ZnONPassmb) (average sizes of 10, 30, and 163 nm, respectively), having a core size of 10-15 nm, in the amyloid growth of hen egg white lysozyme (HEWL). We monitored the amyloid growth by electron microscopy as well as Thioflavin-T (ThT) measurement. We observed that ZnONP demonstrated a dose-dependent inhibition of fibrillar amyloid growth of HEWL, with the greatest effect being exhibited by ZnONPST. Such inhibition was also associated with a decrease in cross β-sheet amount, surface hydrophobicity as well as increase of stability of proteins. Furthermore, we observed that ZnONPSTprolonged the nucleation phase and shortened the elongation phase of HEWL amyloid growth. Although pure amyloid caused profound cellular toxicity in both mouse carcinoma N2a and normal cells such as human keratinocytes HaCaT cells, amyloid formed in the presence of ZnONP showed much reduced cellular toxicity. We also observed that the inhibition of amyloid growth was effective when ZnONP was administered during the lag phase. When our amyloid inhibition results were compared with a well-known inhibitor curcumin, we observed that ZnONPSTdemonstrated a better inhibitory effect than curcumin. Overall, here, we reported the inhibitory activity of three different forms of ZnONP to amyloid fibrillation of HEWL and amyloid-mediated cytotoxicity to different extents, while starch-capped ZnONP showed the highest fibrillation inhibitory effect.
authors: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela-769008, Odisha, India.
authors: Deependra Kumar
authors: DK
authors: Ban
authors: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela-769008, Odisha, India.
authors: Subhankar
authors: S
authors: Paul
mesh_terms: D000682:Amyloid; D000818:Animals; D003474:Curcumin; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D009113:Muramidase; D015034:Zinc Oxide / Q000737:chemistry*
chemical_list: D000682:Amyloid; D009113:Muramidase; D003474:Curcumin; D015034:Zinc Oxide
keywords: Thioflavin-T fluorescence; amyloid; cellular toxicity; circular dichroism; zinc oxide nanoparticles