Neurotoxicity of pre-incubated alpha-synuclein with neutral nanoliposomes on PC12 and SHSY5Y cell lines

Document Type: Article

Authors

1 Department and Center for Biotechnology Research and Student Research Committee, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

2 Cell and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.

3 Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

4 Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK–8000 Aarhus C, Denmark.

5 Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

6 Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

7 Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran

8 Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.

9 Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.

Abstract

Alpha-synuclein (α-Syn) is an abundant protein in the brain with high tendency to convert into toxic aggregated forms that are involved in neurons degeneration in Parkinson's patients (PD). The conversion of α-Syn toward toxic aggregates may associate with bio-membranes and the interaction between α-Syn and bio-mimic liposomes can trigger the neurotoxicity. Some inhibitors of α-Syn aggregation are potential drugs to cure PD; however, they have low stability and solubility at physiological conditions. Using nano-carriers such as nanoliposomes may overcome such defects. Nevertheless, there are few studies on nanoliposomes effects on neuronal cells and α-Syn. Herein; we investigated the neurotoxicity and also fibrinogenesis of neutral charged nanoliposomes. Thin layer evaporation method and the Mini-Extruder set were employed to formulate the nanoliposomes from Dipalmitoylphosphatidylcholine to the size of ≤ 100 nm. Fibrillation and also cytotoxicity of α-Syn treated with different concentrations of nanoliposome were measured by different assays. Neither neurotoxicity nor fibril induction were observed when α-Syn treated with different concentrations of nanoliposome (35-3000 µM). These results well indicated that nanoliposome at the concentrations, which are needed to drug delivery, not only be able to prevent fibrillation process, but also have no considerable toxic effects on the neural cells.

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