ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2020
AKT2 maintains brain endothelial claudin-5 expression and selective activation of IR/AKT2/FOXO1-signaling reverses barrier dysfunction.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026Review
- Exercise-induced modulation of astrocyte in Alzheimer's disease: mechanisms and therapeutic implications.Frontiers in physiology · 2026Review
- Plasma proteomics uncovers divergent molecular signatures in ischemic stroke and intracerebral hemorrhage.Biomarker research · 2025Article
- Claudin 5 Across the Vascular Landscape: From Blood-Tissue Barrier Regulation to Disease Mechanisms.Cells · 2025Review
- Deficiency in N-cadherin-Akt3 signaling impairs the blood-brain barrier.Cell reports · 2025Article
- Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Endothelial Myosin IIA Is Required for the Maintenance of Blood-Brain Barrier Integrity.Cells · 2024Article
- Differential effects of AKT1 and AKT2 on sleep-wake activity under basal conditions and in response to LPS challenge in mice.Sleep and biological rhythms · 2024Article
- Determination of Solute Permeability of Microvascular Endothelial Cell Monolayers In Vitro.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Edema and lymphatic clearance: molecular mechanisms and ongoing challenges.Clinical science (London, England : 1979) · 2023Review
- Lung infection by Pseudomonas aeruginosa induces neuroinflammation and blood-brain barrier dysfunction in mice.Journal of neuroinflammation · 2023Article
- Lung infection by P. aeruginosa induces neuroinflammation and blood-brain barrier dysfunction in mice.Research square · 2023Article
- Lack of adducin impairs the stability of endothelial adherens and tight junctions and may be required for cAMP-Rac1-mediated endothelial barrier stabilization.Scientific reports · 2022Article
- FOXO1 represses sprouty 2 and sprouty 4 expression to promote arterial specification and vascular remodeling in the mouse yolk sac.Development (Cambridge, England) · 2022Article
- Loss of SOX18/CLAUDIN5 disrupts the pulmonary endothelial barrier in ventilator-induced lung injury.Frontiers in physiology · 2022Article
- Astrocytes and pericytes attenuate severely injured patient plasma mediated expression of tight junction proteins in endothelial cells.PloS one · 2022Article
- 'A picture is worth a thousand words': The use of microscopy for imaging neuroinflammation.Clinical and experimental immunology · 2021Review
- Foxo1-induced miR-92b down-regulation promotes blood-brain barrier damage after ischaemic stroke by targeting NOX4.Journal of cellular and molecular medicine · 2021Article
- Immunohistological Examination of AKT Isoforms in the Brain: Cell-Type Specificity That May Underlie AKT's Role in Complex Brain Disorders and Neurological Disease.Cerebral cortex communications · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammation-induced blood-brain barrier (BBB) dysfunction and microvascular leakage are associated with a host of neurological disorders. The tight junction protein claudin-5 (CLDN5) is a crucial protein necessary for BBB integrity and maintenance. CLDN5 is negatively regulated by the transcriptional repressor FOXO1, whose activity increases during impaired insulin/AKT signaling. Owing to an incomplete understanding of the mechanisms that regulate CLDN5 expression in BBB maintenance and dysfunction, therapeutic interventions remain underdeveloped. Here, we show a novel isoform-specific function for AKT2 in maintenance of BBB integrity. We identified that AKT2 during homeostasis specifically regulates CLDN5-dependent barrier integrity in brain microvascular endothelial cells (BMVECs) and that intervention with a selective insulin-receptor (IR) agonist, demethylasterriquinone B1 (DMAQ-B1), rescued IL-1β-induced AKT2 inactivation, FOXO1 nuclear accumulation, and loss of CLDN5-dependent barrier integrity. Moreover, DMAQ-B1 attenuated preclinical CLDN5-dependent BBB dysfunction in mice subjected to experimental autoimmune encephalomyelitis. Taken together, the data suggest a regulatory role for IR/AKT2/FOXO1-signaling in CLDN5 expression and BBB integrity 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.