Metabolomics-driven exploration of sphingosine 1-phosphate mechanisms in refractory epilepsy

IF 5.1 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2025-05-09 DOI:10.1016/j.nbd.2025.106953

Xinyu Ben , Chang Li , Jiaqi Liu , Ting Liu, Jingyi Tong, Qifu Li

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引用次数: 0

Abstract

This study aims to investigate the role of sphingosine 1-phosphate (S1P) in refractory epilepsy (RE) and elucidate its underlying molecular mechanisms. We employed metabolomics technology to analyze serum metabolites and gene expression patterns in individuals with RE. Additional omics analyses were conducted using cellular and animal models to explore the specific functions of S1P and related metabolic pathways. Our findings demonstrated that ACER3/SphK1/S1P play protective roles in maintaining mitochondrial structure and function. These elements were shown to mitigate neuronal hyperexcitability and protect against neuronal damage. By elucidating the dysregulation of metabolic pathways associated with disease onset and progression, our research illuminated the impact of abnormal sphingolipid metabolism and gene expression variances on the manifestation and progression of RE. This research underscores the critical impact of abnormal sphingolipid metabolism on RE development and progression. The insights gained from this study provide a foundation for developing targeted pharmaceutical interventions and symptomatic treatments for individuals with RE.

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代谢组学对难治性癫痫中鞘氨醇1-磷酸机制的研究。

本研究旨在探讨鞘氨醇1-磷酸（S1P）在难治性癫痫（RE）中的作用并阐明其潜在的分子机制。我们利用代谢组学技术分析了RE患者的血清代谢物和基因表达模式，并利用细胞和动物模型进行了额外的组学分析，以探索S1P的具体功能和相关代谢途径。我们的研究结果表明，ACER3/SphK1/S1P在维持线粒体结构和功能方面具有保护作用。这些元素被证明可以减轻神经元的过度兴奋性并防止神经元损伤。通过阐明与疾病发生和进展相关的代谢途径失调，我们的研究阐明了鞘脂代谢异常和基因表达变异对RE的表现和进展的影响。本研究强调了鞘脂代谢异常对RE发生和进展的重要影响。从本研究中获得的见解为开发针对RE患者的针对性药物干预和对症治疗提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.