CHAPTER 10: Regulation of Oligodendrocyte Differentiation: New Targets for Drug Discovery in Remyelination
Published:18 Jun 2019
The formation of myelin is one of the main characteristics of cell differentiation in central nervous system (CNS) development. In physiological conditions, oligodendrocytes are the only myelin-forming cells in the CNS. During development, oligodendrocytes derive from oligodendrocyte precursor cells (OPCs). These represent important numbers in the adult CNS, in a relatively quiescent state. After damage, such as in multiple sclerosis (MS), OPCs react and increase their capacity to form new oligodendrocytes and myelin: this process is known as spontaneous remyelination. To date, the therapeutic arsenal to treat MS is composed only of immune-modulators that modify the evolution of the disease but do not replace the myelin lost and the dead oligodendrocytes. The very first clinical trial showing positive results with a remyelinating agent in MS were released in 2017, opening a door for an unmet need for current neurology: the use of (re)meylinating agents in clinics, normally in combination with immune-modulators, to attack MS in its neuropathological facet, too. In the present chapter we review: the basics of oligodendrogliogenesis and myelin formation during development; pathways in the adult involved in oligodendrogliogenesis that could be targets for future therapeutic designs in search of (re)myelination; and, finally, all the putative (re)myelinating agents currently in the pipeline.