ArticleScience advances2020
Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Structure-activity profiling of indazole-based derivatives as spinster homolog 2 (Spns2)-dependent S1P release inhibitors.Bioorganic & medicinal chemistry letters · 2027Article
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- Huntington's disease vasculopathy is barrier-type-selective and arteriolar-dominant with spatially-coupled astrogliosis and reversible by S1pr1 stimulation.Nature communications · 2026Article
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- Neurovascular unit remodeling: focusing on glial cells in stroke injury and recovery.Frontiers in cellular neuroscience · 2026Review
- MFSD2A: a molecular nexus linking blood-brain barrier, lipid metabolism, and ischemia-reperfusion injury.Cellular & molecular biology letters · 2025Review
- The MDM2-p53 axis regulates norrin/frizzled4 signaling and blood-CNS barrier function.Science signaling · 2025Article
- Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice.Biomolecules & therapeutics · 2025Article
- Caveolae-Mediated Transcytosis and Its Role in Neurological Disorders.Biomolecules · 2025Review
- SPHK1/S1PR1/PPAR-α axis restores TJs between uroepithelium providing new ideas for IC/BPS treatment.Life science alliance · 2025Article
- Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.Nature communications · 2025Article
- Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood-brain barrier function in neurological diseases.Frontiers in neuroscience · 2025Review
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- Neural Regulation of Vascular Development: Molecular Mechanisms and Interactions.Biomolecules · 2024Review
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Sphingosine-1-phosphate Signalling in Aneurysmal Subarachnoid Haemorrhage: Basic Science to Clinical Translation.Translational stroke research · 2024Review
- Siponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways.International journal of molecular sciences · 2024Article
- TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.Neuroscience bulletin · 2024Article
- Microbiota-derived imidazole propionate inhibits type 2 diabetic skin wound healing by targeting SPNS2-mediated S1P transport.iScience · 2023Article
- Imidazole-based sphingosine-1-phosphate transporter Spns2 inhibitors.Bioorganic & medicinal chemistry letters · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To maintain brain homeostasis, a unique interface known as the blood-brain barrier (BBB) is formed between the blood circulation and the central nervous system (CNS). Major facilitator superfamily domain-containing 2a (Mfsd2a) is a specific marker of the BBB. However, the mechanism by which Mfsd2a influences the BBB is poorly understood. In this study, we demonstrated that Mfsd2a is essential for sphingosine-1-phosphate (S1P) export from endothelial cells in the brain. We found that Mfsd2a and Spinster homolog 2 (Spns2) form a protein complex to ensure the efficient transport of S1P. Furthermore, the S1P-rich microenvironment in the extracellular matrix (ECM) in the vascular endothelium dominates the formation and maintenance of the BBB. We demonstrated that different concentrations of S1P have different effects on BBB integrity. These findings help to unravel the mechanism by which S1P regulates BBB and also provide previously unidentified insights into the delivery of neurological drugs in the CNS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.