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

Accepted version
Peer-reviewed

Type

Article

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Authors

Gonzalez, GA 
Hofer, MP 
Syed, YA 
Amaral, AI 
Rundle, J 

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.

Description

Keywords

StemCellInstitute

Journal Title

Scientific Reports

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

6

Publisher

Nature Publishing Group
Sponsorship
Medical Research Council (MC_PC_12009)
Department of Health (via National Institute for Health Research (NIHR)) (CS-2015-15-023)
This work was supported by grants from Wings for Life and the UK Multiple Sclerosis Society. M.R.N.K. holds an NIHR CL award and a Sir David and Isobel Walker fellowship. G.A.G. was supported by CONICYT (Becas Chile) scholarship, and M.P.H. was supported by a Sir David and Isobel Walker studentship. Research in the author’s laboratory is supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust Medical Research Council Cambridge Stem Cell Institute