Retinoic acid regulates myelin formation in the peripheral nervous system

Glia
Maria-Jesus LatasaJose Miguel Cosgaya

Abstract

Understanding the mechanisms that control myelin formation is essential for the development of demyelinating diseases treatments. All-trans-retinoic acid (RA) plays an essential role during the development of the nervous system as a potent regulator of morphogenesis, cell growth, and differentiation. In this study, we show that RA is also a potent inhibitor of peripheral nervous system (PNS) myelination. RA acts through its binding to RA receptors (RAR) and retinoid X receptors (RXR), two members of the superfamily of nuclear receptors that act as ligand-dependent transcription factors. Schwann cells (SCs) express all retinoid receptors during the relevant stages of myelin formation. Through the activation of RXR, RA produces an upregulation of Krox20, a SC-specific regulatory transcription factor that plays a central role during myelination. Krox20 upregulation translates into Mbp and Mpz overexpression, therefore blocking myelin formation. This increase in myelin protein expression is accompanied by the induction of an adaptive ER stress response. At the same time, through a RAR-dependent mechanism, RA downregulates myelin-associated glycoprotein, which also contributes to the dysmyelinating effect of the retinoid.

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Citations

Sep 8, 2012·Journal of Clinical Immunology·André HeinenPatrick Küry
Apr 26, 2012·ACS Chemical Biology·Sung-Wook JangJames Inglese
Mar 10, 2011·PloS One·Maria-Jesus Latasa, Jose Miguel Cosgaya
Sep 14, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ferdinand KayaAndre Mazabraud
Sep 18, 2014·Clinical Neuropharmacology·Elisabeth ChroniDionysios Tsambaos
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Feb 7, 2012·Journal of Chemical Neuroanatomy·René KönigJörg Mey
Apr 27, 2011·Annals of Neurology·David KremerPatrick Küry
Mar 2, 2012·Glia·Caroline ApraLaurence Decker
Apr 18, 2016·Biochimica Et Biophysica Acta·Maria-Jesus LatasaJose Miguel Cosgaya
Apr 26, 2011·Experimental Neurology·Hui ZhangAnna Williams
Dec 24, 2014·Tissue & Cell·Nazila NiapourMohammad Reza Gholami
Jul 15, 2017·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Tomohiro IshiiKazuhiko Watabe
Aug 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Susu MaoBin Yu
Jul 25, 2021·International Journal of Molecular Sciences·Marwa El SouryGiulia Ronchi

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