Abstract
Major facilitator superfamily (MFS) is the maximum and most diversified membrane transporter, acting as uniporters, symporters and antiporters. MFS is considered to have a good development potential in the transport of drugs for the treatment of brain diseases. The major facilitator superfamily domain containing protein 2a (Mfsd2a) is a member of MFS. Mfsd2a-knockout mice have shown a marked decrease of docosahexaenoic acid (DHA) level in brain, exhibiting neuron loss, microcephaly and cognitive deficits, as DHA acts essentially in brain growth and integrity. Mfsd2a has attracted more and more attention in the study of nervous system diseases because of its critical role in maintaining the integrity of the blood-brain barrier (BBB) and transporting DHA, including inhibiting cell transport in central nervous system endothelial cells, alleviating BBB injury, avoiding BBB injury in cerebral hemorrhage model, acting as a carrier etc. Up to now, the clinical research of Mfsd2a in nervous system diseases is rare. This article reviewed the current research progress of Mfsd2a in nervous system diseases. It summarized the physiological functions of Mfsd2a in the occurrence and development of intracranial hemorrhage (ICH), Alzheimer’s disease (AD), sepsis-associated encephalopathy (SAE), autosomal recessive primary microcephaly (MCPH) and intracranial tumor, aiming to provide ideas for the basic research and clinical application of Mfsd2a.
Highlights
As one of the two largest families of membrane transporters (Pao et al, 1998), the major facilitator superfamily (MFS) is the largest and most ubiquitously found family of secondary active membrane carriers (Saier et al, 2014; Finn et al, 2016)
We reviewed the research of major facilitator superfamily domain containing protein 2a (Mfsd2a) in nervous system diseases, such as intracranial hemorrhage (ICH), Alzheimer’s disease (AD), sepsis associated encephalopathy (SAE), autosomal recessive primary microcephaly (MCPH), and intracranial tumor, aiming to provide a reference for the basic research and clinical application of Mfsd2a
The results suggested that the protective effect of Mfsd2a against blood brain barrier (BBB) injury may be achieved by inhibiting vesicular transcytosis after ICH
Summary
As one of the two largest families of membrane transporters (Pao et al, 1998), the major facilitator superfamily (MFS) is the largest and most ubiquitously found family of secondary active membrane carriers (Saier et al, 2014; Finn et al, 2016). To maintain and regulate the integrity and permeability of BBB To avoid BBB injury in cerebral hemorrhage model To promotes brain development and the formation of cognitive abilities To act as a carrier, transporting DHA into the brain. Mfsd2a is expressed in BBB capillary endothelial cells It could transport LPC, which connects long chain fatty acids, into the brain microvascular endothelial cells. Tiwary et al (2018) treated human brain microvascular endothelial cells (HBMECs) with different cytokines known to affect the properties of endothelial barrier, including TGFβ1, bFGF/FGF2 and VEGF, finding that both TGFβ1 and bFGF induced Mfsd2a expression, whereas VEGF inhibited the expression of Mfsd2a gene in HBMECs. The decreased expression of Mfsd2a in patients with BMs may be related to the lack of TGFβ1 and bFGF signaling pathways in pathological conditions.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
