The Role of Major Facilitator Superfamily Domain-Containing 2a in the Central Nervous System

Major facilitator superfamily-domain containing 2a (Mfsd2a) is selectively expressed in vascular endotheliocytes and plays a crucial role in maintaining the integrity of the blood‒brain barrier and the transport of docosahexaenoic acid. It is currently recognized as the only molecule that inhibits endocytosis mediated by caveolae in brain endothelial cells. Mfsd2a gene knockout leads to an increase in the permeability of the blood-brain barrier from embryonic stages to adulthood while maintaining the normal pattern of the vascular network. In Mfsd2a knockout mice, the docosahexaenoic acid content is significantly reduced and associated with neuron loss, resulting in microcephaly and cognitive impairment. Based on the role of Mfsd2a in the central nervous system, it has been preliminarily suggested as a potential therapeutic target for drug delivery to the central nervous system. This paper reviews the current progress in Mfsd2a research and summarizes the physiological functions of Mfsd2a in the central nervous system and its role in the occurrence and development of a variety of neurological diseases.