Revealing how omega-3 fatty acids are transported into the brain
Brain cells are rich in the omega-3 fatty acid docosahexaenoic acid (DHA), which is essential for normal brain growth and function. DHA in the brain comes entirely from the blood. It was not known how DHA crosses the protective blood-brain barrier (BBB) to enter the brain.
The aim of these experiments was to understand lipid transport across the BBD and of disruptions in this process that can lead to birth defects or neurological conditions.
The authors developed a unique Zebrafish model to undertake a range of experiments.
The authors have shown that:
- A member of the major facilitator superfamily (Mfsd2a) is the major transporter for DHA into the brain.
- Mfsd2a is located in the blood-brain barrier.
- There are five single-particle cryo-EM structures of Danio rerio Mfsd2a (drMfsd2a).
- Mfsd2a snapshots detail the flipping mechanism for lipid-LPC from outer to inner membrane leaflet and release for membrane integration on the cytoplasmic side.
- Mfsd2a mutants that disrupt lipid-LPC transport are associated with disease.
Mfsd2a transports omega-3 fatty acids into the brain and may enable researchers to optimize drug delivery via this route.
Nguyen, C., et al., Lipid flipping in the omega-3 fatty-acid transporter. Nature Communications, 2023. 14(1): p. 2571.