Targeting Smoothened as a New Frontier in the Functional Recovery of Central Nervous System Demyelinating Pathologies
Myelin sheaths on vertebrate axons provide protection, vital support and increase the speed of neuronal signals. Myelin degeneration can be caused by viral, autoimmune or genetic diseases. Remyelination is a natural process that restores the myelin sheath and, consequently, neuronal function after a...
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| Veröffentlicht in: | International journal of molecular sciences 2018-11, Vol.19 (11), p.3677 |
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| description | Myelin sheaths on vertebrate axons provide protection, vital support and increase the speed of neuronal signals. Myelin degeneration can be caused by viral, autoimmune or genetic diseases. Remyelination is a natural process that restores the myelin sheath and, consequently, neuronal function after a demyelination event, preventing neurodegeneration and thereby neuron functional loss. Pharmacological approaches to remyelination represent a promising new frontier in the therapy of human demyelination pathologies and might provide novel tools to improve adaptive myelination in aged individuals. Recent phenotypical screens have identified agonists of the atypical G protein-coupled receptor Smoothened and inhibitors of the glioma-associated oncogene 1 as being amongst the most potent stimulators of oligodendrocyte precursor cell (OPC) differentiation in vitro and remyelination in the central nervous system (CNS) of mice. Here, we discuss the current state-of-the-art of studies on the role of Sonic Hedgehog reactivation during remyelination, referring readers to other reviews for the role of Hedgehog signaling in cancer and stem cell maintenance. |
| doi_str_mv | 10.3390/ijms19113677 |
| format | Article |
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Myelin degeneration can be caused by viral, autoimmune or genetic diseases. Remyelination is a natural process that restores the myelin sheath and, consequently, neuronal function after a demyelination event, preventing neurodegeneration and thereby neuron functional loss. Pharmacological approaches to remyelination represent a promising new frontier in the therapy of human demyelination pathologies and might provide novel tools to improve adaptive myelination in aged individuals. Recent phenotypical screens have identified agonists of the atypical G protein-coupled receptor Smoothened and inhibitors of the glioma-associated oncogene 1 as being amongst the most potent stimulators of oligodendrocyte precursor cell (OPC) differentiation in vitro and remyelination in the central nervous system (CNS) of mice. 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 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| subjects | Animals Axons Cell cycle Cell differentiation Cell division Central nervous system Central Nervous System - parasitology Central Nervous System - pathology Cholesterol - biosynthesis Degeneration Demyelinating Diseases - pathology Demyelinating Diseases - physiopathology Demyelination Genetic disorders Glioma Growth factors Hedgehog protein Humans Ligands Myelin Myelination Neurodegeneration Recovery of Function Review Sheaths Signal Transduction Smoothened Receptor - metabolism Spinal cord Stem cells Stimulators Transcription factors Tumors Vertebrates |
| title | Targeting Smoothened as a New Frontier in the Functional Recovery of Central Nervous System Demyelinating Pathologies |
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