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Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

Gonzalez, Ginez A., Hofer, Matthias P., Syed, Yasir A., Amaral, Ana I., Rundle, Jon, Rahman, Saifur, Zhao, Chao and Kotter, Mark R. N. 2016. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system. Scientific Reports 6 , 31599. 10.1038/srep31599

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Abstract

Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 16 February 2017
Date of Acceptance: 15 June 2016
Last Modified: 15 Jul 2019 11:41
URI: http://orca.cf.ac.uk/id/eprint/98200

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