ArticlePloS one2013
Inhibition of glycogen synthase kinase 3β promotes tight junction stability in brain endothelial cells by half-life extension of occludin and claudin-5.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 122 citations in OpenAlex.
- Acute amyloid-β exposure disrupts insulin signaling in hCMEC/D3 blood-brain barrier endothelial cells.Fluids and barriers of the CNS · 2026Article
- Endocytic turnover of endothelial cell-membrane proteins as a driver of rat blood-brain barrier specialization and dysfunction.iScience · 2026Article
- Orally bioavailable CBResearch square · 2026Article
- EHD4 and ASAP2 are critical negative regulators of the claudin-5-based endothelial barrier.The FEBS journal · 2026Article
- Rapamycin Prevents Sulfate-Reducing Bacteria-Induced Effects on Snail and GSK-3 and Impaired Intestinal Barrier.Microorganisms · 2026Article
- Environmental enrichment and physical exercise prevent stress-induced social avoidance and blood-brain barrier alterations via Fgf2.Nature communications · 2026Article
- Acute amyloid-β exposure disrupts insulin signaling in blood-brain barrier endothelial cell culture models.Research square · 2026Article
- Reduced SNHG16 promotes sepsis-induced intestinal injury via the miR-15a-5p/AKT3 axis.BMC gastroenterology · 2026Article
- Glycogen synthase kinase-3: the master switch driving neurodegeneration in Alzheimer's disease and Parkinson's disease.Archives of toxicology · 2025Review
- Across Barriers: Blood-Brain and Gut Barrier Signaling in Psychiatric Disorders.Journal of neurochemistry · 2025Review
- Claudin 5 Across the Vascular Landscape: From Blood-Tissue Barrier Regulation to Disease Mechanisms.Cells · 2025Review
- Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Endothelial Neurogranin Regulates Blood-Brain Barrier Permeability via Modulation of the AKT Pathway.Molecular neurobiology · 2025Article
- Cerebral Small Vessel Disease: Therapeutic Approaches Targeting Neuroinflammation, Oxidative Stress, and Endothelial Dysfunction.Current issues in molecular biology · 2025Review
- ENPP1 induces blood-brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer.Neuro-oncology · 2025Article
- Potential Mechanisms of Tetramethylpyrazine in the Treatment of Traumatic Brain Injury Based on Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations, and in vivo Experiments.International journal of general medicine · 2025Article
- Physical activity and glioblastoma: a paradigm shift in neuro-oncology therapy.Frontiers in oncology · 2025Review
- The Basic Requirement of Tight Junction Proteins in Blood-Brain Barrier Function and Their Role in Pathologies.International journal of molecular sciences · 2024Review
- Mouse embryonic stem cell-derived blood-brain barrier model: applicability to studying antibody triggered receptor mediated transcytosis.Fluids and barriers of the CNS · 2023Article
- The CLDN5 gene at the blood-brain barrier in health and disease.Fluids and barriers of the CNS · 2023Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroinflammatory conditions often involve dysfunction of the Blood-Brain Barrier (BBB). Therefore, identifying molecular targets that can maintain barrier fidelity is of clinical importance. We have previously reported on the anti-inflammatory effects that glycogen synthase kinase 3β (GSK3β) inhibition has on primary human brain endothelial cells. Here we show that GSK3β inhibitors also promote barrier tightness by affecting tight junction (TJ) protein stability. Transendothelial electrical resistance (TEER) was used to evaluate barrier integrity with both pharmacological inhibitors and mutants of GSK3β. Inhibition of GSK3β produced a gradual and sustained increase in TEER (as much as 22% over baseline). Analysis of subcellular membrane fractions revealed an increase in the amount of essential tight junction proteins, occludin and claudin-5, but not claudin-3. This phenomenon was attributed to a decrease in TJ protein turnover and not transcriptional regulation. Using a novel cell-based assay, inactivation of GSK3β significantly increased the half-life of occludin and claudin-5 by 32% and 43%, respectively. A correlation was also established between the enhanced association of β-catenin with ZO-1 as a function of GSK3β inhibition. Collectively, our findings suggest the possibility of using GSK3β inhibitors as a means to extend the half-life of key tight junction proteins to promote re-sealing of the BBB during neuroinflammation.
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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.