Non-steroidal anti-inflammatory drug indometacin enhances endogenous remyelination

Anna Preisner, Stefanie Albrecht, Qiao Ling Cui, Stephanie Hucke, Julia Ghelman, Christine Hartmann, Makoto Mark Taketo, Jack Antel, Luisa Klotz, Tanja Kuhlmann

    Research output: Contribution to journalArticle

    20 Scopus citations

    Abstract

    Multiple sclerosis is the most frequent demyelinating disease in the CNS that is characterized by inflammatory demyelinating lesions and axonal loss, the morphological correlate of permanent clinical disability. Remyelination does occur, but is limited especially in chronic disease stages. Despite effective immunomodulatory therapies that reduce the number of relapses the progressive disease phase cannot be prevented. Therefore, promotion of neuroprotective and repair mechanisms, such as remyelination, represents an attractive additional treatment strategy. A number of pathways have been identified that may contribute to impaired remyelination in MS lesions, among them the Wnt/β-catenin pathway. Here, we demonstrate that indometacin, a non-steroidal anti-inflammatory drug (NSAID) that has been also shown to modulate the Wnt/β-catenin pathway in colorectal cancer cells promotes differentiation of primary human and murine oligodendrocytes, myelination of cerebellar slice cultures and remyelination in cuprizone-induced demyelination. Our in vitro experiments using GSK3β inhibitors, luciferase reporter assays and oligodendrocytes expressing a mutant, dominant stable β-catenin indicate that the mechanism of action of indometacin depends on GSK3β activity and β-catenin phosphorylation. Indometacin might represent a promising treatment option to enhance endogenous remyelination in MS patients.

    Original languageEnglish (US)
    Pages (from-to)247-261
    Number of pages15
    JournalActa neuropathologica
    Volume130
    Issue number2
    DOIs
    StatePublished - Aug 25 2015

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    Keywords

    • GSK3β
    • Indometacin
    • Multiple sclerosis
    • Oligodendrocytes
    • Remyelination
    • β-Catenin

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine
    • Clinical Neurology
    • Cellular and Molecular Neuroscience

    Cite this

    Preisner, A., Albrecht, S., Cui, Q. L., Hucke, S., Ghelman, J., Hartmann, C., Taketo, M. M., Antel, J., Klotz, L., & Kuhlmann, T. (2015). Non-steroidal anti-inflammatory drug indometacin enhances endogenous remyelination. Acta neuropathologica, 130(2), 247-261. https://doi.org/10.1007/s00401-015-1426-z