Critical Role of Endothelial Lysophosphatidylcholine Transporter Mfsd2a in Maintaining Blood–Brain Barrier Integrity and Delivering Omega 3 PUFA to the Brain
Parnova Rg
Abstract
The protein Mfsd2a (Major Facilitator Superfamily Domain Containing 2a), a specific Na+-dependent transporter of lysophosphatidylcholine (lysoPC) esterified by omega-3 polyunsaturated fatty acids (PUFA), is selectively expressed in the endothelium of brain capillaries. This review summarizes current concepts on the molecular mechanisms of its functioning in endothelial cells and the role of transported lipids in the inhibition of caveolin-dependent transcytosis and maintaining a low permeability of the blood–brain barrier (BBB). A special focus is on the Mfsd2a-mediated lysoPC transfer as it is a major route of entry into the brain and retina for docosahexaenoic acid and other omega-3 PUFA essential for the normal development and functioning of the CNS and visual system. The protective role of Mfsd2a in various CNS neuropathologies is also discussed, as well as the prospects for developing Mfsd2a-based therapeutic strategies to increase the bioavailability of essential PUFA and to deliver the drugs that do not penetrate the BBB to brain tissue.