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Review
. 2016 Sep;283(Pt B):512-30.
doi: 10.1016/j.expneurol.2016.03.019. Epub 2016 Mar 23.

Extracellular cues influencing oligodendrocyte differentiation and (re)myelination

Natalie A Wheeler  1 , Babette Fuss  2
Affiliations
Review

Extracellular cues influencing oligodendrocyte differentiation and (re)myelination

Natalie A Wheeler et al. Exp Neurol. 2016 Sep.

Abstract

There is an increasing number of neurologic disorders found to be associated with loss and/or dysfunction of the CNS myelin sheath, ranging from the classic demyelinating disease, multiple sclerosis, through CNS injury, to neuropsychiatric diseases. The disabling burden of these diseases has sparked a growing interest in gaining a better understanding of the molecular mechanisms regulating the differentiation of the myelinating cells of the CNS, oligodendrocytes (OLGs), and the process of (re)myelination. In this context, the importance of the extracellular milieu is becoming increasingly recognized. Under pathological conditions, changes in inhibitory as well as permissive/promotional cues are thought to lead to an overall extracellular environment that is obstructive for the regeneration of the myelin sheath. Given the general view that remyelination is, even though limited in human, a natural response to demyelination, _targeting pathologically 'dysregulated' extracellular cues and their downstream pathways is regarded as a promising approach toward the enhancement of remyelination by endogenous (or if necessary transplanted) OLG progenitor cells. In this review, we will introduce the extracellular cues that have been implicated in the modulation of (re)myelination. These cues can be soluble, part of the extracellular matrix (ECM) or mediators of cell-cell interactions. Their inhibitory and permissive/promotional roles with regard to remyelination as well as their potential for therapeutic intervention will be discussed.

Keywords: CNS injury; Extracellular; Multiple sclerosis; Myelin; Neuropsychiatric diseases; Oligodendrocyte; Regeneration; Remyelination; Signaling.

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Figures

Figure 1
Figure 1. Schematic representation of extracellular cues acting as permissive/promotional (top; green) and/or inhibitory (bottom; red) cues at the different stages along the OLG lineage
Note that most cues play multiple roles by affecting OLGs at more than one stage along the lineage. In some cases, cues may exert inhibitory effects at one stage while playing a promotional/permissive role at another stage (see for example: GPR17 ligands and FGF). *myelin thickness only; ** process outgrowth only.
See this image and copyright information in PMC

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References

    1. Abbracchio MP, Burnstock G, Boeynaems J-M, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev. 2006;58:281–341. - PMC - PubMed
    1. Almeida RG, Lyons DA. On the resemblance of synapse formation and CNS myelination. Neuroscience. 2014;276:98–108. - PubMed
    1. Ara J, See J, Mamontov P, Hahn A, Bannerman P, Pleasure D, Grinspan JB. Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis. J Neurosci Res. 2008;86:125–135. - PubMed
    1. Arellano RO, Sanchez-Gomez MV, Alberdi E, Canedo-Antelo M, Chara JC, Palomino A, Perez-Samartin A, Matute C. Axon-to-Glia Interaction Regulates GabaA Receptor Expression in Oligodendrocytes. Mol Pharmacol. 2015 Nov 4; [Epub ahead of print] - PubMed
    1. Armstrong RC, Le TQ, Flint NC, Vana AC, Zhou Y-X. Endogenous cell repair of chronic demyelination. J Neuropathol Exp Neurol. 2006;65:245–256. - PMC - PubMed

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