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使用转基因技术研究氧化铈纳米颗粒在阿尔茨海默病中的治疗潜力。

Investigation of therapeutic potential of cerium oxide nanoparticles in Alzheimer's disease using transgenic .

作者信息

Sundararajan Vignesh, Venkatasubbu G Devanand, Sheik Mohideen Sahabudeen

机构信息

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203 India.

Department of Physics and Nanotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203 India.

出版信息

3 Biotech. 2021 Apr;11(4):159. doi: 10.1007/s13205-021-02706-x. Epub 2021 Mar 6.

Abstract

In the current study, the therapeutic potential of cerium oxide nanoparticles (nCeO) was investigated in a human tau (htau) model of Alzheimer's disease (AD), using as an in vivo model. nCeO synthesised via the hydroxide-mediated approach were characterised using Fourier transform infrared (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD) analyses and Raman spectroscopy. Characterisation studies confirmed the formation of pure cubic-structured nCeO and showed that the particles were spherically shaped, with an average size between 20 and 25 nm. The synthesised nCeO were then administered as part of the diet to transgenic for one month, at 0.1 and 1 mM concentrations, and its effect on the biochemical levels of superoxide dismutase (SOD), acetylcholinesterase (AChE), and the climbing activity of flies were studied in a pan-neuronal model (elav; htau) of AD. Using an eye-specific model of htau expression (GMR; htau), the effect of nCeO on htau and autophagy-related (ATG) gene expression was also studied. Dietary administration of nCeO at a concentration of 1 mM restored the activity of SOD similar to that of control, but both concentrations of nCeO failed to modulate the level of AChE, and did not elicit any significant improvements in the climbing activity of elav; htau flies. Moreover, nCeO at a concentration of 1 mM significantly affected the climbing activity of elav; htau flies. nCeO also elicited a significant decrease in htau gene expression at both concentrations and increased the mRNA expression of key autophagy genes ATG1 and ATG18. The results therefore indicate that nCeO aids in replenishing the levels of SOD and tau clearance via the activation of autophagy.

摘要

在当前研究中,使用果蝇作为体内模型,研究了氧化铈纳米颗粒(nCeO)在阿尔茨海默病(AD)的人tau(htau)模型中的治疗潜力。通过氢氧化物介导的方法合成的nCeO,采用傅里叶变换红外光谱(FTIR)、透射电子显微镜(TEM)、X射线衍射(XRD)分析和拉曼光谱进行表征。表征研究证实形成了纯立方结构的nCeO,并表明颗粒呈球形,平均尺寸在20至25纳米之间。然后将合成的nCeO以0.1和1 mM的浓度作为饮食的一部分给予转基因果蝇一个月,并在AD的全神经元模型(elav;htau)中研究其对超氧化物歧化酶(SOD)、乙酰胆碱酯酶(AChE)生化水平以及果蝇攀爬活性的影响。使用htau表达的眼睛特异性模型(GMR;htau),还研究了nCeO对htau和自噬相关(ATG)基因表达的影响。以1 mM浓度饮食给予nCeO可恢复SOD活性至与对照相似的水平,但两种浓度的nCeO均未能调节AChE水平,并且未引起elav;htau果蝇攀爬活性的任何显著改善。此外,1 mM浓度的nCeO显著影响elav;htau果蝇的攀爬活性。两种浓度的nCeO还均显著降低了htau基因表达,并增加了关键自噬基因ATG1和ATG18的mRNA表达。因此,结果表明nCeO通过激活自噬有助于补充SOD水平和清除tau。

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