oa CNS Remyelination – Can We Wrap It Up? – Regulators of Neural Stem/Precursor Cells in the Process of Myelin Regeneration

Enhancing the regeneration of myelin sheaths in the central nervous system has been identified as an important therapeutic strategy to ameliorate the devastating consequences of demyelination that occur in diseases such as multiple sclerosis (MS). For remyelination to occur successfully oligodendrocyte precursor cells (OPCs) need to be recruited into areas of demyelination, engage with axons, and differentiate into myelin forming oligodendrocytes. However, in the context of demyelinating disease the differentiation of OPCs into oligodendrocytes often fails, resulting in chronic demyelination despite the presence of OPCs.

Important insight has been gained from studies investigating the interaction of stem/precursor cells with the distinct environment of demyelinating lesions. These suggest that successful regeneration depends on a signaling environment conducive to remyelination, which is provided in the context of acute inflammation. On the other hand it has been proposed that the specific environment of MS lesions contains factors that exert inhibitory effects on OPC differentiation. The pattern by which remyelination inducers and inhibitors are expressed in multiple sclerosis lesions may determine a window of opportunity during which oligodendrocyte precursor cells can successfully differentiate. This presentation will discuss evidence of inhibitory mechanisms associated with early stages of MS lesion development. Based on these findings it will outline novel approaches for enhancing remyelination in the central nervous system.