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5-HT_1F受体激素诱导线粒体生物发生并增加大脑微血管内皮细胞中的细胞功能

Natalie E Scholpa^1,2, Epiphani C Simmons^1,3, Austin D Thompson^1,2,4

¹Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, United States.

Frontiers in cellular neuroscience

|March 21, 2024

概括

拉斯米迪坦是一种5西胺1F受体 (5-HT_1FR) 激动剂,促进线粒体生物发生和血管恢复. 这表明,对于涉及线粒体和血管功能障碍的中枢神经系统疾病有潜在的治疗益处.

科学领域:

神经科学是一个神经科学.
线粒体生物学线粒体生物学
血管生物学血管生物学

背景情况:

中枢神经系统 (CNS) 疾病通常涉及血管和线粒体功能障碍.
已被证明,5-基胺1F受体 (5-HT_1FR) 激素诱导线粒体生物发生 (MB) 在各种组织中,包括中枢神经系统.

研究的目的:

研究拉斯米迪坦 (lasmiditan) 是一种选择性5-HT_1FR激动剂,它可以改善血管和线粒体功能的机制.
为了检查拉斯米迪坦对小鼠大脑微血管内皮细胞 (mBMEC) 的影响.

主要方法:

主要的mbMEC被用拉斯米迪坦治疗.
评估线粒体功能 (氧气消耗,蛋白质水平,密度).
评估了内皮细胞迁移,管道形成,屏障功能 (TEER,紧接口) 和信号通路 (VE-Cadherin,Akt-FoxO1).

主要成果:

拉斯米迪坦治疗增加了线粒体生物发生,增强了内皮细胞迁移和管形成.
通过增加TEER和Claudin-5表达,改善了屏障功能.
拉斯米迪坦调节了VE-卡德林-Akt-FoxO1-克劳丁-5信号通路.

结论:

拉斯米迪坦诱导线粒体生物发生,并通过VE-Cadherin-Akt-FoxO1-claudin-5轴增强内皮细胞功能.
拉斯米迪坦为例的5-HT_1FR激素具有通过解决线粒体和血管功能障碍来治疗中枢神经系统疾病的治疗潜力.

关键词:

5-HT1F受体的受体是什么血脑屏障血脑屏障血脑屏障血脑屏障血液脊髓障碍物脊髓障碍物它们是内皮细胞的内皮细胞.拉斯米迪坦拉斯米迪坦拉斯米迪坦线粒体生物发生是线粒体生物发生.血管的恢复血管的恢复

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