Regulation of Oligodendrocyte Differentiation: New Targets for Drug Discovery in Remyelination
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.