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雷帕霉素在癫痫中 mTOR 信号通路及其抑制剂的研究进展。

Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy.

机构信息

Department of Gerontology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.

Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.

出版信息

Brain Behav. 2023 Jun;13(6):e2995. doi: 10.1002/brb3.2995. Epub 2023 May 23.


DOI:10.1002/brb3.2995
PMID:37221133
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10275542/
Abstract

INTRODUCTION: Epilepsy is one of the most common and serious brain syndromes and has adverse consequences on a patient's neurobiological, cognitive, psychological, and social wellbeing, thereby threatening their quality of life. Some patients with epilepsy experience poor treatment effects due to the unclear pathophysiological mechanisms of the syndrome. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway is thought to play an important role in the onset and progression of some epilepsies. METHODS: This review summarizes the role of the mTOR signaling pathway in the pathogenesis of epilepsy and the prospects for the use of mTOR inhibitors. RESULTS: The mTOR pathway functions as a vital mediator in epilepsy development through diverse mechanisms, indicating that the it has great potential as an effective target for epilepsy therapy. The excessive activation of mTOR signaling pathway leads to structural changes in neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, and is closely associated with tau upregulation in epilepsy. A growing number of studies have demonstrated that mTOR inhibitors exhibit significant antiepileptic effects in both clinical applications and animal models. Specifically, rapamycin, a specific inhibitor of TOR, reduces the intensity and frequency of seizures. Clinical studies in patients with tuberous sclerosis complex have shown that rapamycin has the function of reducing seizures and improving this disease. Everolimus, a chemically modified derivative of rapamycin, has been approved as an added treatment to other antiepileptic medicines. Further explorations are needed to evaluate the therapeutic efficacy and application value of mTOR inhibitors in epilepsy. CONCLUSIONS: Targeting the mTOR signaling pathway provides a promising prospect for the treatment of epilepsy.

摘要

简介:癫痫是最常见和最严重的脑部综合征之一,对患者的神经生物学、认知、心理和社会健康都有不良影响,从而威胁到他们的生活质量。由于该综合征的病理生理机制尚不清楚,一些癫痫患者的治疗效果不佳。雷帕霉素靶蛋白(mTOR)通路的失调被认为在一些癫痫的发病和进展中起着重要作用。

方法:本综述总结了 mTOR 信号通路在癫痫发病机制中的作用以及 mTOR 抑制剂的应用前景。

结果:mTOR 通路通过多种机制作为癫痫发展的重要介质发挥作用,表明其作为癫痫治疗的有效靶点具有巨大潜力。mTOR 信号通路的过度激活导致神经元结构改变,抑制自噬,加重神经元损伤,影响苔藓纤维发芽,增强神经元兴奋性,增加神经炎症,并与癫痫中的 tau 上调密切相关。越来越多的研究表明,mTOR 抑制剂在临床应用和动物模型中均具有显著的抗癫痫作用。具体来说,雷帕霉素,一种 TOR 的特异性抑制剂,可降低癫痫发作的强度和频率。在结节性硬化症患者的临床研究中,雷帕霉素具有减少癫痫发作和改善该疾病的功能。雷帕霉素的化学修饰衍生物依维莫司已被批准作为其他抗癫痫药物的附加治疗药物。需要进一步探索来评估 mTOR 抑制剂在癫痫中的治疗效果和应用价值。

结论:靶向 mTOR 信号通路为癫痫的治疗提供了有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ac/10275542/802676d61956/BRB3-13-e2995-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ac/10275542/802676d61956/BRB3-13-e2995-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ac/10275542/802676d61956/BRB3-13-e2995-g001.jpg

相似文献

[1]
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[10]
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本文引用的文献

[1]
Protective effect of N-acetyl cysteine on the mitochondrial dynamic imbalance in temporal lobe epilepsy: Possible role of mTOR.

Neuropeptides. 2022-12

[2]
Time and age dependent regulation of neuroinflammation in a rat model of mesial temporal lobe epilepsy: Correlation with human data.

Front Cell Dev Biol. 2022-9-13

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Cells. 2022-8-23

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Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy.

Cell Biol Int. 2022-11

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Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy.

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Antiepileptic Effect and Safety Profile of Rapamycin in Pediatric Patients With Tuberous Sclerosis Complex.

Front Neurol. 2022-4-29

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Neurol Res. 2022-10

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Epilepsy Behav. 2022-5

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