Omega-3 fatty acids may help treatments cross blood-brain barrier

New images of a molecule that shuttles omega-3 fatty acids into the brain may open a doorway for delivering neurological therapeutics to the brain, according to new research published in the journal Nature.

A major challenge in treating neurological diseases is getting treatments across the blood-brain barrier, a layer of tightly packed cells that lines the brain's blood vessels and zealously blocks toxins, pathogens, and some nutrients from entering the brain. This layer also blocks many drugs that are otherwise promising candidates to treat neurological disorders, the researchers said.

Essential nutrients like omega-3 fatty acids require the assistance of dedicated transporter proteins that specifically recognize them and get them across this barrier.

 "The transporters are like bouncers at a club, only letting molecules with invites or backstage passes in," said Rosemary Cater, PhD, first author of the study and a Simons Society Fellow in the Mancia Lab at Columbia University Vagelos College of Physicians and Surgeons, in a statement.

Understanding what MFSD2A looks like and how it pulls omega-3 fatty acids across the blood-brain barrier may provide information to better design treatments, Carter said.

To visualize MFSD2A, Cater used a technique called single-particle cryo-electron microscopy. For cryo-EM analysis, protein molecules are suspended in a thin layer of ice under an electron microscope. Powerful cameras take millions of pictures of the proteins from countless angles which can then be pieced together to construct a 3D map. In this map, researchers can build a 3D model of the protein, putting each atom in its place.

Researchers then used the 3D model of the protein as a starting point to run computational simulations that revealed how the transporter moves and adapts its shape to release omega-3 fatty acids into the brain. The research team then tested and confirmed hypotheses derived from the structure and the computational simulations on how MFSD2A works to pinpoint specific parts of the protein that are important.

The research team is now investigating how the transporter first recognizes omega-3 fatty acids from the bloodstream.

Our study has already given us tremendous insight into how MFSD2A delivers omega-3s to the brain,” Carter said, “and we are really excited to see where our results lead to.”