Abstract
On the assembly of myelin and how such knowledge may aid in improving the therapeutic treatment of MS
Myelin, the fatty insulation layer around nerve cells, sustains damage in patients suffering from multiple sclerosis (MS), among others due to inflammation. Importantly, eventual regeneration of myelin fails. To understand the underlying mechanism, it is important to know how the myelin membranes are formed in ‘normal’ conditions. This knowledge will be imperative to develop novel molecular tools for ‘rebuilding’ the protective myelin coat in MS lesions.
Among others, this research project has revealed new insight as to how the two major myelin proteins, MBP and PLP, can be affected in the process of myelin assembly. For example, when the production of syntaxin 4, a well-known anchor protein in transport processes, is blocked in the precursor cells of oligodendrocytes, the production of MBP halts. We also discovered that the transport of PLP changes when in more mature oligodendrocytes, MAL protein – a transport-regulating protein - is expressed. Furthermore, factors from outside of the cell may also affect the production of myelin. For example, the inflammation mediator TNFα, present in MS lesions, influences the cytoskeleton in such a way that MBP fails to reach the myelin.
This study provides new and detailed insight into molecular mechanisms that regulate the localization of the main myelin components and hence, the assembly of myelin. These results will be beneficial in the development of new therapeutic treatments for MS.
Myelin, the fatty insulation layer around nerve cells, sustains damage in patients suffering from multiple sclerosis (MS), among others due to inflammation. Importantly, eventual regeneration of myelin fails. To understand the underlying mechanism, it is important to know how the myelin membranes are formed in ‘normal’ conditions. This knowledge will be imperative to develop novel molecular tools for ‘rebuilding’ the protective myelin coat in MS lesions.
Among others, this research project has revealed new insight as to how the two major myelin proteins, MBP and PLP, can be affected in the process of myelin assembly. For example, when the production of syntaxin 4, a well-known anchor protein in transport processes, is blocked in the precursor cells of oligodendrocytes, the production of MBP halts. We also discovered that the transport of PLP changes when in more mature oligodendrocytes, MAL protein – a transport-regulating protein - is expressed. Furthermore, factors from outside of the cell may also affect the production of myelin. For example, the inflammation mediator TNFα, present in MS lesions, influences the cytoskeleton in such a way that MBP fails to reach the myelin.
This study provides new and detailed insight into molecular mechanisms that regulate the localization of the main myelin components and hence, the assembly of myelin. These results will be beneficial in the development of new therapeutic treatments for MS.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Supervisors/Advisors |
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| Award date | 4-Apr-2016 |
| Place of Publication | [Groningen] |
| Publisher | |
| Print ISBNs | 978-90-367-8698-0 |
| Electronic ISBNs | 978-90-367-8697-3 |
| Publication status | Published - 2016 |