Study of novel bioactive molecules to promote oligodendrocyte differentiation and myelin formation.
Despite the huge advances in immunological therapies in recent years, there is currently no treatment to repair the myelin sheath that is destroyed in MS or to regenerate oligodendrocytes. Promoting this repair could be beneficial in counteracting the disability associated with MS. The aim of this project is to analyse the effects of hitherto little studied molecules, microRNAs and bioactive lipids, in the differentiation of oligodendrocyte precursor cells and the formation of myelin, in order to better understand the pathogenesis of MS and to identify potential new therapeutic targets.
MS is an inflammatory disease characterised by the destruction of the myelin sheath surrounding neurons. Despite immense progress in recent years in the field of immunological therapies, there is currently no treatment available to repair the myelin sheath that is destroyed in MS or to regenerate oligodendrocytes. Promoting this repair could be beneficial in counteracting MS-related disability. Furthermore, the mechanism of oligodendrocyte maturation and myelin formation remains incompletely elucidated and it is not yet clear which molecules can promote or block these processes.The aim of this project is to analyse the effects and mechanisms of action of hitherto little studied molecules (microRNAs, identified in the cerebrospinal fluid of MS patients) and bioactive lipids (N-ethanolamines) in the differentiation of oligodendrocyte precursor cells and myelin formation. We will study the effect of these molecules in different cell models, first in vitro and then in a more complex model called 'organotypic cultures' isolated from newborn rat brain, combining neurons and oligodendrocytes. Finally, we will establish the mechanism of action of these molecules by identifying their molecular target within the cells. This project will provide a better understanding of the function of these molecules involved in the pathogenesis of MS and identify new potential therapeutic targets.
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