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法呢醇脑转录组学在中枢神经系统炎症性脱髓鞘中的作用。

Farnesol brain transcriptomics in CNS inflammatory demyelination.

机构信息

Department of Biological Sciences, Boise State University, Boise, ID 83725, USA.

Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99202, USA.

出版信息

Clin Immunol. 2023 Oct;255:109752. doi: 10.1016/j.clim.2023.109752. Epub 2023 Sep 4.

Abstract

BACKGROUND

Farnesol (FOL) prevents the onset of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).

OBJECTIVE

We examined the transcriptomic profile of the brains of EAE mice treated with daily oral FOL using next-generation sequencing (RNA-seq).

METHODS

Transcriptomics from whole brains of treated and untreated EAE mice at the peak of EAE was performed.

RESULTS

EAE-induced mice, compared to naïve, healthy mice, overall showed increased expression in pathways for immune response, as well as an increased cytokine signaling pathway, with downregulation of cellular stress proteins. FOL downregulates pro-inflammatory pathways and attenuates the immune response in EAE. FOL downregulated the expression of genes involved in misfolded protein response, MAPK activation/signaling, and pro-inflammatory response.

CONCLUSION

This study provides insight into the molecular impact of FOL in the brain and identifies potential therapeutic targets of the isoprenoid pathway in MS patients.

摘要

背景

法呢醇(FOL)可预防实验性自身免疫性脑脊髓炎(EAE)的发作,EAE 是多发性硬化症(MS)的一种啮齿动物模型。

目的

我们使用下一代测序(RNA-seq)检查了用每日口服 FOL 治疗的 EAE 小鼠大脑的转录组图谱。

方法

对处于 EAE 高峰期的经处理和未经处理的 EAE 小鼠的全脑进行了转录组学分析。

结果

与健康的未处理的对照相比,EAE 诱导的小鼠总体上表现出免疫反应途径的表达增加,以及细胞因子信号通路的增加,同时细胞应激蛋白的表达下调。FOL 下调促炎途径并减弱 EAE 中的免疫反应。FOL 下调了参与错误折叠蛋白反应、MAPK 激活/信号传导和促炎反应的基因的表达。

结论

本研究深入了解了 FOL 在大脑中的分子作用,并确定了异戊烯途径在 MS 患者中的潜在治疗靶点。

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