Researchers Detail How Omega-3 Fatty Acids Enter the Brain

Singapore, June 16, 2021 – Researchers involved in a collaborative study have detailed the structure and function of a key transport protein, MFSD2A, which facilitates the entry of omega-3 fatty acids into the brain and eyes. The findings, published in the journal Nature, offer insights that could help in designing drugs for neurological diseases capable of crossing the blood-brain barrier.

Omega-3 fatty acids, like DHA, are vital for brain and eye development. They are converted in the liver into a lysolipid form to cross the blood-brain and blood-retina barriers. The MFSD2A protein, located on the membrane of endothelial cells forming these barriers, acts as a molecular gateway for DHA. However, the precise mechanism of how MFSD2A mediates this transport remained unclear.

Using cryo-electron microscopy and computer simulations, the research team determined the atomic-level structure of MFSD2A. "If we knew what MFSD2A looked like, we could solve this mystery and use the information to design neurotherapeutics that could hijack this molecular gateway," explained Rosemary Cater, the paper's first author from Columbia University.

David Silver, a professor at Duke-NUS and a study leader, highlighted the significance of the findings. Previous work by his lab identified that mutations in the MFSD2A gene lead to microcephaly, underscoring the protein's critical role. A spin-off company, Travecta Therapeutics, is leveraging this research to develop therapeutics for central nervous system and eye diseases.

The blood-brain barrier typically prevents about 98 percent of drugs from reaching the brain, posing a significant challenge for treating neurological disorders. This enhanced understanding of MFSD2A's function presents a potential pathway to overcome this limitation and develop new therapeutic agents.