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Multiple sclerosis, remyelination and the role of fibronectin

Stoffels, J., 2014, [S.L.]: s.n.. 182 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Josephine Stoffels
Our central nervous system functions, among others, thanks to myelin. Myelin is a fatty layer of insulation among nervous cells, which is produced by specific cells, namely oligodendrocytes. Multiple sclerosis (MS) is a disease that damages myelin. These myelin injuries (lesions) seem largely responsible for the disease burden of MS. Often, these myelin injuries are permanent in MS, but sometimes myelin recovers spontaneously. This suggests that oligodendrocytes are capable of producing new myelin, but usually do not succeed. What signals prevent oligodendrocytes from producing new myelin in MS lesions?
In this thesis, it was investigated how the signal molecule fibronectin influences oligodendrocytes. In these studies, it was discovered that, after myelin injury, fibronectin is ‘automatically’ produced by neighbor cells, including cells named astrocytes. This fibronectin normally promotes recovery of myelin by attracting young progenitor cells of oligodendrocytes. When these progenitors mature to become oligodendrocytes, fibronectin is degraded. However, in MS, fibronectin is not degraded, but accumulates en binds to form aggregates. These fibronectin aggregates were found to impair myelin regeneration by oligodendrocytes. In line with this, fibronectin aggregates are not present in recovered MS lesions. Finally, fibronectin aggregates may stimulate inflammatory reactions of inflammatory cells, named microglia and macrophages. Hence, the observations presented in this thesis suggest that interfering with fibronectin aggregation could contribute to promoting myelin regeneration in MS.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date14-Apr-2014
Place of Publication[S.L.]
Publisher
Print ISBNs978-90-367-6885-6
Electronic ISBNs978-90-367-6885-6
Publication statusPublished - 2014

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