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循环RNA hsa_circ_0000288通过与caprin1蛋白结合和稳定,保护小鼠免受

Lin Guo^1,2, Na Lv^3,4, Jian-Lun Ji^3,4

¹Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. guolin0724@xzhmu.edu.cn.

Acta pharmacologica Sinica

|February 17, 2025

概括

循环RNA hsa_circ_0000288 (circ288) 显示了治疗的治疗潜力. 过度表达circ288在小鼠中减少了发作,神经元损伤,并改善了认知功能,为抗治疗提供了新的途径.

科学领域:

分子生物学分子生物学
神经科学是一个神经科学.
遗传学遗传学是一个

背景情况:

目前的抗药物不足,需要新的治疗策略.
循环RNAs (circRNAs) 正在成为病发病的关键参与者.
识别具有治疗潜力的特定circRNA对于开发新的治疗方法至关重要.

研究的目的:

为了确定抑制缓解期患者病过程的circRNAs.
在症小鼠模型中研究hsa_circ_0000288 (circ288) 的治疗效果.
为了阐明circ288抗作用背后的分子机制.

主要方法:

比较了缓解期和非缓解期患者血清中的circRNA表达特征.
在体内研究中建立了一种因酸诱导的 status epilepticus 小鼠模型.
使用腺相关病毒 (AAV) 载体用于海马体circ288过度表达和基于外体的输送 (EXO-circ288).

主要成果:

在缓解期的患者中,hsa_circ_0000288 (circ288) 度显著升高.
在性小鼠中,Circ288的过度表达改善了神经元损伤,促进了神经发生,减少了发作,改善了情绪和认知.
Circ288直接与caprin1结合,抑制其降解并调节NMDA受体3B的表达.

结论:

Circ288具有显著的神经保护和抗作用,通过素1-NMDA受体3B通路起作用.
外体封装circ288 (EXO-circ288) 提供了一个可行的,非病毒传递方法,具有强大的治疗效果.
Circ288代表了一个有前途的治疗RNA候选人,用于开发新的抗治疗方法.

关键词:

卡普林是一个人.在NMDA受体3B.圆形的RNARNA是一个圆形的RNA.是一种.外基因组封装-外基因组封装在海马体内,海马体

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