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Acta Neuropathologica

, Volume 130, Issue 2, pp 247–261 | Cite as

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
Original Paper

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.

Keywords

Multiple sclerosis Oligodendrocytes Remyelination Indometacin β-Catenin GSK3β 

Notes

Acknowledgments

This study was supported by grants from the German Research Foundation (SFB-TR128-B7; Ku1477/6-1), the Interdisciplinary Clinical Research Center, Münster (IZKF; KuT3/006/11) and the Hertie Foundation (P1130073) to TK.

Supplementary material

401_2015_1426_MOESM1_ESM.pdf (2.4 mb)
Supplementary material 1 (PDF 2421 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Anna Preisner
    • 1
  • Stefanie Albrecht
    • 1
  • Qiao-Ling Cui
    • 2
  • Stephanie Hucke
    • 3
  • Julia Ghelman
    • 1
  • Christine Hartmann
    • 4
  • Makoto Mark Taketo
    • 5
  • Jack Antel
    • 2
  • Luisa Klotz
    • 3
  • Tanja Kuhlmann
    • 1
  1. 1.Institute of NeuropathologyUniversity Hospital MünsterMünsterGermany
  2. 2.Montreal Neurological InstituteMcGill UniversityMontrealCanada
  3. 3.Department of NeurologyUniversity Hospital MünsterMünsterGermany
  4. 4.Institute of Experimental Musculoskeletal MedicineUniversity Hospital MünsterMünsterGermany
  5. 5.Department of PharmacologyKyoto University Graduate School of Medicine Yoshida- Konoé-choKyotoJapan

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