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白藜芦醇通过调节SNHG1/miR-128-3p/SNCA轴促进自噬以改善帕金森病中的神经元损伤。

Resveratrol Promotes Autophagy to Improve neuronal Injury in Parkinson's Disease by Regulating SNHG1/miR-128-3p/SNCA Axis.

作者信息

Shen Dong-Fang, Qi Hui-Ping, Zhang Wei-Na, Sang Wen-Xu

机构信息

Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, No.37, Nangang District, Harbin 150001, China.

出版信息

Brain Sci. 2023 Jul 25;13(8):1124. doi: 10.3390/brainsci13081124.

Abstract

BACKGROUND

Parkinson's disease (PD) is seriously threatening the health and life quality of the elderly, who have a high incidence and high disability rate. Resveratrol (RES) was reported to play a protective role in PD. However, the functions and potential mechanism of RES in PD remain unclear, which need to be further explored.

METHODS

Human neuroblastoma cells (SH-SY5Y and SK-N-SH) were subjected to 1-Methyl-4-phenylpyridium (MPP+) induction to construct a cell model of PD. Cell viability was evaluated using CCK-8. The gene expression was evaluated using qRT-PCR and western blot. Luciferase activity assay and RIP were performed to validate interactions among SNHG1, miR-128-3p and SNCA.

RESULTS

Our results exhibited that RES reduced SNHG1 and SNCA expression but elevated miR-128-3p expression in human neuroblastoma cells upon MPP+ induction. Functionally, RES resulted in the promotion of cell autophagy in MPP+-induced human neuroblastoma cells, while these influences were abolished by SNHG1 overexpression. Mechanistically, SNHG1 could indirectly elevate SNCA expression via sponging miR-128-3p. Moreover, SNCA overexpression reversed SNHG1 silencing-induced cell autophagy in MPP+-induced human neuroblastoma cells upon RES pre-incubation.

CONCLUSIONS

RES prevented MPP+-induced repression of cell autophagy through inhibiting the SNHG1/miR-128-3p/SNCA axis, suggesting that RES might play a preventive effect on PD progression.

摘要

背景

帕金森病(PD)严重威胁老年人的健康和生活质量,其发病率和致残率都很高。据报道,白藜芦醇(RES)在帕金森病中发挥保护作用。然而,RES在帕金森病中的功能和潜在机制仍不清楚,需要进一步探索。

方法

用人神经母细胞瘤细胞(SH-SY5Y和SK-N-SH)进行1-甲基-4-苯基吡啶离子(MPP+)诱导,构建帕金森病细胞模型。使用CCK-8评估细胞活力。使用qRT-PCR和蛋白质免疫印迹法评估基因表达。进行荧光素酶活性测定和RNA免疫沉淀(RIP)以验证SNHG1、miR-128-3p和α-突触核蛋白(SNCA)之间的相互作用。

结果

我们的结果显示,在MPP+诱导下,RES降低了人神经母细胞瘤细胞中SNHG1和SNCA的表达,但提高了miR-128-3p的表达。在功能上,RES促进了MPP+诱导的人神经母细胞瘤细胞中的细胞自噬,而SNHG1的过表达消除了这些影响。机制上,SNHG1可通过海绵吸附miR-128-3p间接提高SNCA的表达。此外,在RES预孵育后,SNCA的过表达逆转了MPP+诱导的人神经母细胞瘤细胞中SNHG1沉默诱导的细胞自噬。

结论

RES通过抑制SNHG1/miR-128-3p/SNCA轴预防MPP+诱导的细胞自噬抑制,表明RES可能对帕金森病进展起到预防作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e36/10452706/704e6e821340/brainsci-13-01124-g001.jpg

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