Nuclear receptors and differentiation of oligodendrocyte precursor cells

Abstract

Oligodendrocytes are the cells responsible for myelin formation during development and in adulthood, both for normal myelin turnover and myelin repair. These highly specialized cells derive from the oligodendrocyte precursor cells (OPCs), through a complex differentiation process involving genetic and epigenetic regulation mechanisms, which switch the phenotype from a migratory and replicative precursor to a mature post-mitotic cell. The process is regulated by a plethora of molecules, involving neurotransmitters, growth factors, hormones and other small molecules, and is mainly driven by nuclear receptors (NRs). NRs are transcription factors with heterogeneous ligand-dependent and independent actions which differ for the cell target, the responsive gene and the formation of NR homo- or heterodimers. This chapter highlights the role of NRs in regulating OPC differentiation, also in view of drug discovery strategies aimed at targeting pathological conditions which interfere with both developmental myelination and remyelination in adulthood.

Keywords: Myelin; Nuclear receptor; Oligodendrocyte precursor cell; Remyelination; Thyroid hormone.