Mfsd2a是必不可少的欧米茄-3脂肪酸 - - 多可萨赫萨赫赛诺酸的载体
Long N Nguyen1, Dongliang Ma2, Guanghou Shui3
1Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore.
Nature
|May 16, 2014
概括
含有2a (Mfsd2a) 蛋白质的主要促进者超级家族域被确定为大脑中多可萨赫萨酸 (DHA) 吸收的主要载体. 这一发现揭示了Mfsd2a在大脑发育和功能中的关键作用.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 多可萨赫萨酸 (DHA) 是一种omega-3脂肪酸,对大脑生长和认知功能至关重要.
- DHA在大脑脂中高度缩,但不能在大脑中新合成,因此需要通过血脑屏障进行运输.
- 控制大脑中DHA吸收的机制在很大程度上是未知的.
研究的目的:
- 为了确定关键的载体,负责Docosahexaenoic酸 (DHA) 吸收到大脑.
- 阐明DHA通过血脑屏障运输的机制和生理意义.
主要方法:
- 使用生物信息学和表达分析识别Mfsd2a作为潜在的载体.
- 产生和分析Mfsd2a-Knockout小鼠以评估DHA水平和神经功能.
- 在体外基于细胞的测定以确定Mfsd2a.a的运输基质和机制.
- 来自淘汰赛和野生型小鼠的大脑组织的脂质组分析.
主要成果:
- 确定Mfsd2a是大脑中DHA吸收的主要载体,仅在血脑屏障内皮表达.
- Mfsd2a淘汰赛的小鼠表现出大脑DHA水平显著降低,神经元损失,认知缺陷和小头症.
- 发现Mfsd2a以依赖于的方式以 lysophosphatidylcholine (LPC) 的形式运输DHA,特别是具有14个碳或更多的乙烯链的LPC.
- 在Mfsd2a介导的运输中,LPC的-zwitterionic头组对Mfsd2a介导运输至关重要.
结论:
- Mfsd2a是中介光酸丁结合的DHA被吸收到大脑中的必不可少的载体.
- Mfsd2a对大脑发育,神经元完整性和认知功能起着至关重要的作用.
- 血衍生型酸胆对大脑生长和功能至关重要,Mfsd2a是关键的调解器.
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