Myelin Regeneration: From Experimental Models to Multiple Sclerosis Lesions
Brahim Nait Oumesmar
Brain and Spine Institute - ICM Paris (France)
Oligodendrocytes are cells within the central nervous system (CNS) that produce myelin, a multilamellar structures insulating axons and allowing the rapid conduction of action potentials. These cells are derived from oligodendrocyte precursor cells (OPCs), a class of progenitors highly abundant during development but also persistent in the adult brain, where they contribute to myelin regeneration in demyelinating diseases, like multiple sclerosis (MS). While oligodendrocyte regeneration could be very efficient in experimental models of demyelination, this regenerative process is heterogeneous and ultimately fails with MS progression. There is now substantial evidence that myelin helps to maintain axonal integrity and that the loss of myelin results in axonal degeneration. These observations support the hypothesis that enhancing remyelination would be an effective means to prevent axonal loss and increasing disability in MS patients. Understanding the mechanisms regulating adult OPCs differentiation is of a vital importance for the identification of new targets promoting remyelination. In this presentation, I will discuss our recent finding on the functional roles of the transcription factors Olig2 and Sox17 in oligodendrocyte development and regeneration in experimental models of demyelination and MS lesions.