Publication

GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis

Qin, J., Sikkema, A. H., van der Bij, K., de Jonge, J. C., Klappe, K., Nies, V., Jonker, J. W., Kok, J. W., Hoekstra, D. & Baron, W., 11-Oct-2017, In : The Journal of Neuroscience. 37, 41, p. 9925-9938 14 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Qin, J., Sikkema, A. H., van der Bij, K., de Jonge, J. C., Klappe, K., Nies, V., ... Baron, W. (2017). GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis. The Journal of Neuroscience, 37(41), 9925-9938. https://doi.org/10.1523/JNEUROSCI.0103-17.2017

Author

Qin, Jing ; Sikkema, Arend H. ; van der Bij, Kristine ; de Jonge, Jenny C. ; Klappe, Karin ; Nies, Vera ; Jonker, Johan W. ; Kok, Jan Willem ; Hoekstra, Dick ; Baron, Wia. / GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A : Implications for Multiple Sclerosis. In: The Journal of Neuroscience. 2017 ; Vol. 37, No. 41. pp. 9925-9938.

Harvard

Qin, J, Sikkema, AH, van der Bij, K, de Jonge, JC, Klappe, K, Nies, V, Jonker, JW, Kok, JW, Hoekstra, D & Baron, W 2017, 'GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis', The Journal of Neuroscience, vol. 37, no. 41, pp. 9925-9938. https://doi.org/10.1523/JNEUROSCI.0103-17.2017

Standard

GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A : Implications for Multiple Sclerosis. / Qin, Jing; Sikkema, Arend H.; van der Bij, Kristine; de Jonge, Jenny C.; Klappe, Karin; Nies, Vera; Jonker, Johan W.; Kok, Jan Willem; Hoekstra, Dick; Baron, Wia.

In: The Journal of Neuroscience, Vol. 37, No. 41, 11.10.2017, p. 9925-9938.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Qin J, Sikkema AH, van der Bij K, de Jonge JC, Klappe K, Nies V et al. GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis. The Journal of Neuroscience. 2017 Oct 11;37(41):9925-9938. https://doi.org/10.1523/JNEUROSCI.0103-17.2017


BibTeX

@article{f521a4218b54446fa3768ba3def4fdc3,
title = "GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis",
abstract = "Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides (i.e., cell surface lipids with a potential to modulate signaling pathways) could counteract fibronectin-mediated inhibition of OPC maturation. Exclusive exposure of rat oligodendrocytes to GD1a, but not other gangliosides, overcomes aggregated fibronectin-induced inhibition of myelin membrane formation, in vitro, and OPC differentiation in fibronectin aggregate containing cuprizone-induced demyelinated lesions in male mice. GD1a exerts its effect on OPCs by inducing their proliferation and, at a late stage, by modulating OPC maturation. Kinase activity profiling revealed that GD1a activated a protein kinase A (PKA)-dependent signaling pathway and increased phosphorylation of the transcription factorcAMPresponse element-binding protein. Consistently, the effect of GD1a in restoring myelin membrane formation in the presence of fibronectin aggregates was abolished by the PKA inhibitor H89, whereas the effect of GD1a was mimicked by the PKA activator dibutyryl-cAMP. Together, GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation by activating a PKA-dependent signaling pathway. Given the persistent presence of fibronectin aggregates in MS lesions, ganglioside GD1a might act as a potential novel therapeutic tool to selectively modulate the detrimental signaling environment that precludes remyelination.",
keywords = "fibronectin, ganglioside, multiple sclerosis, oligodendrocyte, remyelination, OLIGODENDROCYTE PROGENITOR CELLS, CENTRAL-NERVOUS-SYSTEM, CYCLIC-AMP, DEMYELINATED LESIONS, MEMBRANE FORMATION, ANCHORED PROTEINS, RAFT-ASSOCIATION, PRECURSOR CELLS, IN-VITRO, DIFFERENTIATION",
author = "Jing Qin and Sikkema, {Arend H.} and {van der Bij}, Kristine and {de Jonge}, {Jenny C.} and Karin Klappe and Vera Nies and Jonker, {Johan W.} and Kok, {Jan Willem} and Dick Hoekstra and Wia Baron",
note = "Copyright {\circledC} 2017 the authors.",
year = "2017",
month = "10",
day = "11",
doi = "10.1523/JNEUROSCI.0103-17.2017",
language = "English",
volume = "37",
pages = "9925--9938",
journal = "The Journal of Neuroscience",
issn = "0270-6474",
publisher = "Oxford University Press",
number = "41",

}

RIS

TY - JOUR

T1 - GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A

T2 - Implications for Multiple Sclerosis

AU - Qin, Jing

AU - Sikkema, Arend H.

AU - van der Bij, Kristine

AU - de Jonge, Jenny C.

AU - Klappe, Karin

AU - Nies, Vera

AU - Jonker, Johan W.

AU - Kok, Jan Willem

AU - Hoekstra, Dick

AU - Baron, Wia

N1 - Copyright © 2017 the authors.

PY - 2017/10/11

Y1 - 2017/10/11

N2 - Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides (i.e., cell surface lipids with a potential to modulate signaling pathways) could counteract fibronectin-mediated inhibition of OPC maturation. Exclusive exposure of rat oligodendrocytes to GD1a, but not other gangliosides, overcomes aggregated fibronectin-induced inhibition of myelin membrane formation, in vitro, and OPC differentiation in fibronectin aggregate containing cuprizone-induced demyelinated lesions in male mice. GD1a exerts its effect on OPCs by inducing their proliferation and, at a late stage, by modulating OPC maturation. Kinase activity profiling revealed that GD1a activated a protein kinase A (PKA)-dependent signaling pathway and increased phosphorylation of the transcription factorcAMPresponse element-binding protein. Consistently, the effect of GD1a in restoring myelin membrane formation in the presence of fibronectin aggregates was abolished by the PKA inhibitor H89, whereas the effect of GD1a was mimicked by the PKA activator dibutyryl-cAMP. Together, GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation by activating a PKA-dependent signaling pathway. Given the persistent presence of fibronectin aggregates in MS lesions, ganglioside GD1a might act as a potential novel therapeutic tool to selectively modulate the detrimental signaling environment that precludes remyelination.

AB - Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides (i.e., cell surface lipids with a potential to modulate signaling pathways) could counteract fibronectin-mediated inhibition of OPC maturation. Exclusive exposure of rat oligodendrocytes to GD1a, but not other gangliosides, overcomes aggregated fibronectin-induced inhibition of myelin membrane formation, in vitro, and OPC differentiation in fibronectin aggregate containing cuprizone-induced demyelinated lesions in male mice. GD1a exerts its effect on OPCs by inducing their proliferation and, at a late stage, by modulating OPC maturation. Kinase activity profiling revealed that GD1a activated a protein kinase A (PKA)-dependent signaling pathway and increased phosphorylation of the transcription factorcAMPresponse element-binding protein. Consistently, the effect of GD1a in restoring myelin membrane formation in the presence of fibronectin aggregates was abolished by the PKA inhibitor H89, whereas the effect of GD1a was mimicked by the PKA activator dibutyryl-cAMP. Together, GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation by activating a PKA-dependent signaling pathway. Given the persistent presence of fibronectin aggregates in MS lesions, ganglioside GD1a might act as a potential novel therapeutic tool to selectively modulate the detrimental signaling environment that precludes remyelination.

KW - fibronectin

KW - ganglioside

KW - multiple sclerosis

KW - oligodendrocyte

KW - remyelination

KW - OLIGODENDROCYTE PROGENITOR CELLS

KW - CENTRAL-NERVOUS-SYSTEM

KW - CYCLIC-AMP

KW - DEMYELINATED LESIONS

KW - MEMBRANE FORMATION

KW - ANCHORED PROTEINS

KW - RAFT-ASSOCIATION

KW - PRECURSOR CELLS

KW - IN-VITRO

KW - DIFFERENTIATION

U2 - 10.1523/JNEUROSCI.0103-17.2017

DO - 10.1523/JNEUROSCI.0103-17.2017

M3 - Article

C2 - 28899916

VL - 37

SP - 9925

EP - 9938

JO - The Journal of Neuroscience

JF - The Journal of Neuroscience

SN - 0270-6474

IS - 41

ER -

ID: 47993047