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PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2020-09-11 , DOI: 10.2147/ijn.s258311
Jie Gao 1, 2 , Xiaohan Chen 1 , Tianjun Ma 1 , Bin He 1 , Peng Li 1 , Yucheng Zhao 1 , Yuejin Ma 1 , Jianhua Zhuang 1 , You Yin 1
Affiliation  

Purpose: Alzheimer’s disease (AD) is a neurodegenerative disorder that manifests as abnormal behavior and a progressive decline in memory. Although the pathogenesis of AD is due to the excessive deposition of amyloid β protein (Aβ) outside the neurons in the brain, evidence suggests that tau proteins may be a better target for AD therapy. In neurodegenerative diseases, a decrease in autophagy results in the failure to eliminate abnormally deposited or misfolded proteins. Therefore, induction of autophagy may be an effective way to eliminate tau proteins in the treatment of AD. We investigated the effects of polyethylene glycol (PEG)-ceramide nanomicelles on autophagy and on tau proteins in N2a, a murine neuroblastoma metrocyte cell line.
Methods: Ceramide is a sphingolipid bioactive molecule that induces autophagy. PEG-ceramide is a polymer that is composed of the hydrophobic chain of ceramide and the hydrophilic chain of PEG-2000. In this study, we prepared PEG-ceramide nanomicelles that were 10– 20 nm in size and had nearly neutral zeta potential.
Results: The results show that PEG-ceramide nanomicelles caused an increase in the LC3-II/LC3-I ratio, while p62 protein levels decreased. Confocal microscopy revealed a significant increase in the number of dots corresponding to autophagosomes and autolysosomes, which indicated autophagic activation. Moreover, PEG-ceramide nanomicelles induced tau degradation in N2a cells through autophagy.
Conclusion: In summary, we have confirmed that PEG-ceramide nanomicelles enhanced autophagic flux and degraded overexpressed human tau proteins in N2a cells by regulating the autophagy pathway. Thus, PEG-ceramide nanomicelles show great promise as agents to induce autophagy and degrade tau proteins in the treatment of AD.

Keywords: Alzheimer’s disease, autophagosomes, lysosome, nano-carrier, autophagic flux


中文翻译:

PEG-神经酰胺纳米胶束在 N2a 细胞中诱导自噬和降解 Tau 蛋白

目的:阿尔茨海默病 (AD) 是一种神经退行性疾病,表现为行为异常和记忆力进行性下降。尽管 AD 的发病机制是由于大脑神经元外的淀粉样 β 蛋白 (Aβ) 过度沉积,但有证据表明 tau 蛋白可能是 AD 治疗的更好靶点。在神经退行性疾病中,自噬减少导致无法消除异常沉积或错误折叠的蛋白质。因此,诱导自噬可能是消除 tau 蛋白治疗 AD 的有效途径。我们研究了聚乙二醇 (PEG)-神经酰胺纳米胶束对小鼠神经母细胞瘤巨细胞系 N2a 中自噬和 tau 蛋白的影响。
方法:神经酰胺是一种诱导自噬的鞘脂类生物活性分子。PEG-神经酰胺是由神经酰胺的疏水链和PEG-2000的亲水链组成的聚合物。在这项研究中,我们制备了尺寸为 10-20 nm 且具有接近中性 zeta 电位的 PEG-神经酰胺纳米胶束。
结果:结果表明,PEG-神经酰胺纳米胶束导致 LC3-II/LC3-I 比率增加,而 p62 蛋白水平降低。共聚焦显微镜显示与自噬体和自溶酶体相对应的点数量显着增加,这表明自噬激活。此外,PEG-神经酰胺纳米胶束通过自噬诱导 N2a 细胞中的 tau 降解。
结论:总之,我们已经证实,PEG-神经酰胺纳米胶束通过调节自噬途径增强了 N2a 细胞中的自噬通量并降解过表达的人 tau 蛋白。因此,PEG-神经酰胺纳米胶束在 AD 治疗中作为诱导自噬和降解 tau 蛋白的药物具有很大的前景。

关键词:阿尔茨海默病,自噬体,溶酶体,纳米载体,自噬通量
更新日期:2020-09-11
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