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Inflammation and dephosphorylation of the tight junction protein occludin in an experimental model of multiple sclerosis
Abstract
Multiple sclerosis (MS) is a disease of the CNS in which inflammation, demyelination and neurodegeneration contribute to its initiation and progression. A frequently employed model of MS is experimental autoimmune encephalomyelitis (EAE). Here, to gain new insights into the disease process, an analysis of proteins in extracts of lumbar spinal cord from naïve and EAE rats was undertaken. The data mainly confirm that inflammation and blood-brain barrier (BBB) breakdown are the major hallmarks of disease in this model. Given their importance in the BBB, junctional proteins were further investigated. Occludin, a protein localizing to tight junctions in brain endothelial cells, showed strikingly increased migration in EAE when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This increased migration was mimicked by in vitro phosphatase treatment, implying its dephosphorylation in EAE. Occludin dephosphorylation coincided with the onset of inflammation, slightly preceding visible signs of disease, and was just prior to apparent changes in BBB permeability. These findings suggest occludin is a target for signaling processes in EAE, perhaps regulating the response of the BBB to the inflammatory environment as seen in MS.
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“the severity of symptoms for MS and AD have been shown to be tightly coupled with BBB integrity, with research indicating that onset and progression of symptoms correlates strongly with BBB disruption”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Morgan et al., 2007
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Metadata
- Authors
- Morgan, L., Shah, B., Rivers, L. E., Barden, L., Groom, A. J., Chung, R., Higazi, D., Desmond, H., Smith, T., & Staddon, J. M.
- Affiliations
- University College London (GB)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 147
- Issue
- 3
- Pages
- 664-673
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2095205887
- Cited by
- 118
- References
- 58
- Citations by year
- 2025: 6 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 11 · 2012: 8
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- multiple sclerosis, experimental autoimmune encephalomyelitis, occludin, tight junction proteins, protein dephosphorylation, blood-brain barrier disruption, myelitis, demyelination, phosphatase treatment, brain endothelial cells, blood-brain barrier permeability
- MeSH terms
- Animals, Disease Models, Animal, Encephalitis, Encephalomyelitis, Autoimmune, Experimental, Female, Membrane Proteins, Phosphoric Monoester Hydrolases, Phosphorylation, Rats, Inbred Lew, Mass Spectrometry, Spinal Cord, Electrophoresis, Gel, Two-Dimensional, Tight Junctions, Endothelial Cells, Immunoprecipitation, Rats, Occludin
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