“Nature” published an article revealing the function of an important “regulatory switch” of the blood-brain barrier

This week, the top academic journal Nature published an online research paper by Professor Feng Liang's team at Stanford University, revealing the structure and functional mechanism of the blood-brain barrier lipid transport protein MFSD2A. This discovery helps to design drugs to regulate the permeability of the blood-brain barrier.


MFSD2A is a phospholipid transporter that is responsible for the uptake of docosahexaenoic acid into the brain in endothelial cells that make up the blood-brain barrier. Docosahexaenoic acid is better known as DHA, which is essential for the development and performance of the brain. Mutations that affect the function of MFSD2A can cause a developmental problem called microcephaly syndrome.

The lipid transport ability of MFSD2A also means that this protein is closely related to the integrity of the blood-brain barrier. Previous studies have found that when its activity is reduced, the blood-brain barrier will leak. Therefore, MFSD2A is regarded as a promising regulatory switch when it is necessary to cross the blood-brain barrier to deliver therapeutic drugs into the brain.

In this study, Professor Feng Liang's team used cryo-electron microscopy technology to obtain the high-resolution structure of mouse MFSD2A, revealing its unique extracellular domain and substrate binding cavity.

Combining functional analysis and molecular dynamics simulations, the researchers also identified the conserved sodium binding sites in the structure of MFSD2A, revealing potential lipid entry pathways, and helping to understand why specific MFSD2A mutations cause microcephaly syndrome.


Post time: Sep-01-2021