title: Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system.
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.
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Ginez A
authors.initials: GA
authors.lastname: Gonzalez
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Hofer
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Yasir A
authors.initials: YA
authors.lastname: Syed
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Amaral
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Rundle
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Saifur
authors.initials: S
authors.lastname: Rahman
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Department of Clinical Neurosciences, Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK.
authors.forename: Mark R N
authors.initials: MRN
authors.lastname: Kotter
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D013629:Tamoxifen