The Molecular Basis for Remyelination Failure in Multiple Sclerosis
Myelin sheaths in the central nervous system (CNS) insulate axons and thereby allow saltatory nerve conduction, which is a prerequisite for complex brain function. Multiple sclerosis (MS), the most common inflammatory autoimmune disease of the CNS, leads to the destruction of myelin sheaths and the...
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| Format: | Article |
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MDPI AG
2019-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/825 |
| _version_ | 1797715531478859776 |
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| author | Joel Gruchot Vivien Weyers Peter Göttle Moritz Förster Hans-Peter Hartung Patrick Küry David Kremer |
| author_facet | Joel Gruchot Vivien Weyers Peter Göttle Moritz Förster Hans-Peter Hartung Patrick Küry David Kremer |
| author_sort | Joel Gruchot |
| collection | DOAJ |
| description | Myelin sheaths in the central nervous system (CNS) insulate axons and thereby allow saltatory nerve conduction, which is a prerequisite for complex brain function. Multiple sclerosis (MS), the most common inflammatory autoimmune disease of the CNS, leads to the destruction of myelin sheaths and the myelin-producing oligodendrocytes, thus leaving behind demyelinated axons prone to injury and degeneration. Clinically, this process manifests itself in significant neurological symptoms and disability. Resident oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) are present in the adult brain, and can differentiate into mature oligodendrocytes which then remyelinate the demyelinated axons. However, for multiple reasons, in MS the regenerative capacity of these cell populations diminishes significantly over time, ultimately leading to neurodegeneration, which currently remains untreatable. In addition, microglial cells, the resident innate immune cells of the CNS, can contribute further to inflammatory and degenerative axonal damage. Here, we review the molecular factors contributing to remyelination failure in MS by inhibiting OPC and NSC differentiation or modulating microglial behavior. |
| first_indexed | 2024-03-12T08:08:07Z |
| format | Article |
| id | doaj.art-b1b4886e72784ae69305c14f62d5802a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:08:07Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b1b4886e72784ae69305c14f62d5802a2023-09-02T19:21:09ZengMDPI AGCells2073-44092019-08-018882510.3390/cells8080825cells8080825The Molecular Basis for Remyelination Failure in Multiple SclerosisJoel Gruchot0Vivien Weyers1Peter Göttle2Moritz Förster3Hans-Peter Hartung4Patrick Küry5David Kremer6Department of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyMyelin sheaths in the central nervous system (CNS) insulate axons and thereby allow saltatory nerve conduction, which is a prerequisite for complex brain function. Multiple sclerosis (MS), the most common inflammatory autoimmune disease of the CNS, leads to the destruction of myelin sheaths and the myelin-producing oligodendrocytes, thus leaving behind demyelinated axons prone to injury and degeneration. Clinically, this process manifests itself in significant neurological symptoms and disability. Resident oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) are present in the adult brain, and can differentiate into mature oligodendrocytes which then remyelinate the demyelinated axons. However, for multiple reasons, in MS the regenerative capacity of these cell populations diminishes significantly over time, ultimately leading to neurodegeneration, which currently remains untreatable. In addition, microglial cells, the resident innate immune cells of the CNS, can contribute further to inflammatory and degenerative axonal damage. Here, we review the molecular factors contributing to remyelination failure in MS by inhibiting OPC and NSC differentiation or modulating microglial behavior.https://www.mdpi.com/2073-4409/8/8/825multiple sclerosisremyelinationoligodendroglial precursor cellsneural stem cellsmicroglia |
| spellingShingle | Joel Gruchot Vivien Weyers Peter Göttle Moritz Förster Hans-Peter Hartung Patrick Küry David Kremer The Molecular Basis for Remyelination Failure in Multiple Sclerosis Cells multiple sclerosis remyelination oligodendroglial precursor cells neural stem cells microglia |
| title | The Molecular Basis for Remyelination Failure in Multiple Sclerosis |
| title_full | The Molecular Basis for Remyelination Failure in Multiple Sclerosis |
| title_fullStr | The Molecular Basis for Remyelination Failure in Multiple Sclerosis |
| title_full_unstemmed | The Molecular Basis for Remyelination Failure in Multiple Sclerosis |
| title_short | The Molecular Basis for Remyelination Failure in Multiple Sclerosis |
| title_sort | molecular basis for remyelination failure in multiple sclerosis |
| topic | multiple sclerosis remyelination oligodendroglial precursor cells neural stem cells microglia |
| url | https://www.mdpi.com/2073-4409/8/8/825 |
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