Mfsd2a对血脑屏障的形成和功能至关重要
Ayal Ben-Zvi1, Baptiste Lacoste1, Esther Kur1
1Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature
|May 16, 2014
概括
科学家们确定Mfsd2a是通过抑制转细胞形成来维持血脑屏障 (BBB) 的关键. 这一发现为改善向中枢神经系统 (CNS) 药物输送提供了潜力.
科学领域:
- 神经科学是一个神经科学.
- 血管生物学 血管生物学
- 发展生物学 发展生物学
背景情况:
- 血脑屏障 (BBB) 保护中枢神经系统 (CNS),但阻碍了药物输送.
- 了解BBB形成是操纵其用于治疗目的的关键.
- 目前对控制BBB完整性的分子机制的知识是有限的.
研究的目的:
- 确定调控建立一个功能性的BBB的分子机制.
- 研究Mfsd2a在BBB形成和功能中的作用.
- 探索中枢神经系统药物输送的治疗影响.
主要方法:
- 在小鼠胚胎中使用了一种新的痕迹注射方法来评估BBB发育.
- 在BBB形成期间选BBB特定基因,重点关注Mfsd2a.
- 使用Mfsd2a的基因切除和电子显微镜来分析BBB的结构和功能.
主要成果:
- 小鼠BBB在胚胎第15.5天 (E15.5) 开始发挥功能.
- Mfsd2a在中枢神经系统的血管中选择性表达,对于BBB完整性至关重要.
- 缺乏Mfsd2a会导致细胞转移的增加和BBB的泄漏,而不会影响血管模式或紧密的结合点.
结论:
- Mfsd2a是BBB功能的关键调节者,主要通过抑制中枢神经系统内皮细胞中的囊泡转细胞.
- 细胞调节Mfsd2a表达,以保持BBB的完整性.
- 向Mfsd2a可能为增强向中枢神经系统药物输送提供新的策略.
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