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Acta Neuropathologica

, Volume 133, Issue 3, pp 489–491 | Cite as

Dimethyl fumarate accelerates peripheral nerve regeneration via activation of the anti-inflammatory and cytoprotective Nrf2/HO-1 signaling pathway

  • Fabian SzepanowskiEmail author
  • Daniel M. Donaldson
  • Hans-Peter Hartung
  • Anne K. Mausberg
  • Christoph Kleinschnitz
  • Bernd C. Kieseier
  • Mark Stettner
Correspondence

Peripheral nerves exhibit a remarkable ability to regenerate; however, there is an unmet need to better understand relevant pathways that could support or even accelerate this process. Fumaric acid esters, especially its dimethyl ester (DMF), are an established treatment option for autoimmune diseases [7]. DMF is known to activate the NF-E2-related factor 2 (Nrf2) transcription factor [8] which is ubiquitously and constitutively expressed and primarily localized in the cytoplasm. Its suppressor, Kelch-like ECH-associated protein 1 (Keap1), prevents Nrf2 from entering the nucleus and acts as an adaptor protein for Nrf2 ubiquitinylation. In case of oxidative or electrophilic stress, Nrf2 is released from Keap1 and translocated into the nucleus to induce antioxidant response element (ARE) gene expression [5]. Additionally, Nrf2 has been demonstrated to induce the expression of heme oxygenase 1 (HO-1) [1], a potent cytoprotective and anti-inflammatory enzyme [9, 10]. An emerging body of...

Keywords

Sciatic Nerve Grip Strength Fumaric Acid Wallerian Degeneration Dimethyl Ester 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with ethical standards

Conflict of interest

FS, DMD, and AKM have nothing to disclose. HPH has received honoraria for consulting and lecturing, travel expenses for attending meetings, and financial support for research from Bayer Health Care, Biogen Idec, Genzyme, GeNeuro, Merck Serono, Novartis, Roche, Sanofi Aventis, and TEVA; CK from Ablynx, Bayer Health Care, Boehringer Ingelheim, Biogen Idec, Biotronik, Daiichi Sankyo, Eisai, Ever Pharma, Genzyme, Merck Serono, Mylan, Novartis, Roche, Sanofi Aventis, Siemens, and TEVA; BCK from Bayer Health Care, Biogen Idec, Merck Serono, Novartis, Genzyme, and TEVA. BCK is currently also employee of Biogen. MS has received honoraria for consulting and lecturing, travel expenses for attending meetings or financial support for research from Bayer Health Care, Biogen Idec, Genzyme, Novartis, Sanofi Aventis, Grifols, and TEVA.

Supplementary material

401_2017_1676_MOESM1_ESM.pdf (124 kb)
Supplementary material 1 (PDF 123 kb)
401_2017_1676_MOESM2_ESM.pdf (693 kb)
Supplementary material 2 (PDF 694 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Fabian Szepanowski
    • 1
    Email author
  • Daniel M. Donaldson
    • 1
  • Hans-Peter Hartung
    • 1
  • Anne K. Mausberg
    • 1
    • 2
  • Christoph Kleinschnitz
    • 2
  • Bernd C. Kieseier
    • 1
  • Mark Stettner
    • 1
    • 2
  1. 1.Department of Neurology, Medical FacultyHeinrich-Heine-UniversityDüsseldorfGermany
  2. 2.Department of Neurology, Medical FacultyUniversity Duisburg-EssenEssenGermany

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