皮罗洛基诺林在脑叶酸缺乏症中的保护作用
Vishal Sangha1, Sara Aboulhassane1, Qing Rui Qu1
1Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Fluids and barriers of the CNS
|November 20, 2023
概括
大脑叶酸缺乏会导致神经炎症和氧化应激. 皮罗洛基诺林 (PQQ) 治疗通过增加叶酸吸收和激活关键信号通路来逆转这些影响.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- 叶酸 (维生素B9) 对于神经发育至关重要,通过叶酸受体α (FRα),质子合叶酸载体 (PCFT) 和减少叶酸载体 (RFC) 运输.
- 大脑叶酸缺乏症 (CFD) 源于血液-脑脊液屏障 (BCSFB) 的叶酸运输受损,与神经炎症,氧化应激和线粒体功能障碍有关.
- 罗基诺林 (PQQ) 表现出抗炎,抗氧化和线粒体生物发生效应,并通过核呼吸因子1 (NRF-1) 上调RFC.
研究的目的:
- 研究叶酸缺乏对大脑炎症和氧化应激反应的影响.
- 检查PQQ在缓解这些异常和增强叶酸运输方面的潜力.
主要方法:
- 主要小鼠质细胞在叶酸缺乏 (FD) 条件下培养,并用PQQ治疗,基因表达 (叶酸载体,炎症/氧化标志物) 和线粒体DNA (mtDNA) 含量通过qPCR进行分析.
- 细胞活性氧物种 (ROS) 水平使用DCFDA测定法进行测量.
- 野生型小鼠接受了FD或对照饮食与PQQ治疗,随后进行脑组织分析.
主要成果:
- 叶酸缺乏增加了炎症和氧化应激标志物,细胞ROS,并降低了质细胞中的mtDNA含量.
- PQQ治疗逆转了这些FD诱导的变化.
- 通过激活PGC-1α/NRF-1信号通路,PQQ增强了RFC表达.
结论:
- 大脑叶酸缺乏导致CFD疾病中出现的神经系统缺陷.
- 通过增加大脑的叶酸吸收和扭转缺乏引起的异常,PQQ显示为CFD相关疾病的治疗剂.
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