Silica Nanoparticles Promote α-Synuclein Aggregation and Parkinson's Disease Pathology.

Xin Yuan,Yingxu Yang,Lanxia Meng,Mingyang He,Danhao Xia,Chaoyang Liu,Zhentao Zhang

doi:10.3389/fnins.2021.807988

Abstract

Silica nanoparticles (SiO2 NPs) are increasingly investigated for their potential in drug delivery systems. However, the neurotoxicity of SiO2 NPs remains to be fully clarified. Previously SiO2 NPs have been reported to be detected in the central nervous system, especially in the dopaminergic neurons which are deeply involved in Parkinson’s disease (PD). In this article, we characterized the effects of SiO2 NPs on inducing PD-like pathology both in vitro and in vivo. Results showed that SiO2 NPs promote more severe hyperphosphorylation and aggregation of α-synuclein, mitochondria impairment, oxidative stress, autophagy dysfunction, and neuronal apoptosis in the α-Syn A53T transgenic mice intranasally administrated with SiO2 NPs compared with the control group. Our findings provide new evidence supporting that SiO2 NPs exposure might have a strong capability of promoting the initiation and development of PD.

Highlights

Silica nanoparticles (SiO2 NPs) are defined as nano-sized (1-100 nm) silicon dioxide
Since the SiO2 NPs used in this study were suspended in DMEM/F12 medium with 10% fetal bovine serum (FBS), we evaluated the hydrodynamic properties by DLS (Figure 1B)
The cells were treated with SiO2 NPs for 24 h before the α-Syn preformed fibrils (PFFs) were added into the medium with lipo2000

Summary

Introduction

Silica nanoparticles (SiO2 NPs) are defined as nano-sized (1-100 nm) silicon dioxide. A lot of approaches are responsible for SiO2 NPs entering the internal environment such as respiratory tract inhalation, digestive tract intake, skin contact, and intratracheal instillation (Guo et al, 2021), and they significantly deteriorate multiple organs and systems (Yamashita et al, 2011; Yoshida et al, 2011; Nabeshi et al, 2012; Inoue et al, 2021) Both in vitro and in vivo studies have proved that SiO2 NPs significantly induce pathological alterations in the brain (You et al, 2018; Wei et al, 2020). SiO2 NPs even manifest neurotoxicity via the gut-brain axis by oral administration (Diao et al, 2021) They promote the deposition of intracellular amyloid-β (Aβ) and hyperphosphorylation of tau in neuro2a neuroblastoma cells. All these results raised the possibility that nanoparticle counts for the onset and development of Alzheimer’s disease (AD) (Yang et al, 2014; Huang et al, 2015)

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