Nudging oligodendrocyte intrinsic signaling to remyelinate and repair: Estrogen receptor ligand effects

The Journal of Steroid Biochemistry and Molecular Biology
Anna J KhalajSeema Tiwari-Woodruff

Abstract

Demyelination in multiple sclerosis (MS) leads to significant, progressive axonal and neuronal degeneration. Currently existing immunosuppressive and immunomodulatory therapies alleviate MS symptoms and slow, but fail to prevent or reverse, disease progression. Restoration of damaged myelin sheath by replenishment of mature oligodendrocytes (OLs) should not only restore saltatory axon conduction, but also provide a major boost to axon survival. Our previous work has shown that therapeutic treatment with the modestly selective generic estrogen receptor (ER) β agonist diarylpropionitrile (DPN) confers functional neuroprotection in a chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS by stimulating endogenous remyelination. Recently, we found that the more potent, selective ERβ agonist indazole-chloride (Ind-Cl) improves clinical disease and motor performance. Importantly, electrophysiological measures revealed improved corpus callosal conduction and reduced axon refractoriness. This Ind-Cl treatment-induced functional remyelination was attributable to increased OL progenitor cell (OPC) and mature OL numbers. At the intracellular signaling level, transition of early to late OPCs requires ERK1/2 signaling, an...Continue Reading

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Citations

Feb 3, 2018·Journal of Cellular and Molecular Medicine·Zhongju ShiShiqing Feng
Nov 15, 2017·Proceedings of the National Academy of Sciences of the United States of America·Mukesh K VarshneyJan-Åke Gustafsson
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Dec 15, 2020·Annals of Clinical and Translational Neurology·Dandan TianXu Liu
Mar 26, 2021·Frontiers in Cellular Neuroscience·Felipe A Bustamante-BarrientosLuis Federico Bátiz
Aug 28, 2020·Brain Research Bulletin·Li Zhang, Handong Wang

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