Abstract
Myelination by oligodendrocytes (OLs) is an important biological process essential for central nervous system (CNS) development and functions. Oligodendroglial lineage cells undergo several morphological and molecular changes at different stages of their lineage progression into myelinating OLs. The transition steps of the oligodendrocyte progenitor cells (OPCs) to myelinating oligodendrocytes are defined by a specific pattern of regulated gene expression, which is under the control of coordinated signaling pathways. Any abnormal development, loss or failure of oligodendrocytes to myelinate axons can lead to several neurodegenerative diseases like multiple sclerosis (MS). MS is characterized by inflammation and demyelination, and current treatments target only the immune component of the disease, but have little impact on remyelination. Recently, several pharmacological compounds enhancing remyelination have been identified and some of them are in clinical trials. Here, we will review the current knowledge on oligodendrocyte differentiation, myelination and remyelination. We will focus on MS as a pathological condition, the most common chronic inflammatory demyelinating disease of the CNS in young adults.
Highlights
Oligodendrocytes (OLs) are the myelinating cells in the central nervous system (CNS) [1]
Most of these molecules are identified as inhibitors of myelination. These inhibitory axonal signals such us Jagged, PSA-NCAM, and LINGO-1, activate various transcriptional regulators such as Hes5, Sox 5/6, and Id2/4, and prevent oligodendrocyte progenitor cells (OPCs) differentiation into myelinating oligodendrocytes [57,58]. Other transcription factors, such as sterol regulatory element binding proteins (SREBPs), regulate the expression of genes involved in lipid synthesis, which is crucial for a proper myelination
The different steps of the remyelination process include OPC activation/proliferation, their migration towards the demyelinated area and their differentiation into myelinating oligodendrocytes [69]. These steps are highly regulated by several mechanisms that recapitulate partially those involved during developmental myelination, such as nuclear receptors and their ligands (LXRs α/β, PPARγ, Vitamin D receptor and RXRs), which are important for remyelination [39,40,41,70]
Summary
Oligodendrocytes (OLs) are the myelinating cells in the central nervous system (CNS) [1] They are generated after an orchestrated process of specification (switch of neural progenitors’ cells from producing neuronal to glial cells), proliferation, migration and differentiation during brain, optic nerve and spinal cord development [2]. 8% of total glial cells and are widely distributed in white matter (WM) and to a less extent in grey matter (GM) [7]. This small fraction of adult OPCs remains in a slowly proliferative quiescent state, contributes to myelin remodeling under physiological conditions and to remyelination following a demyelinating injury.
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