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p38 Mitogen-Activated Protein Kinase Regulates Myelination

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Abstract

The p38 mitogen-activated protein kinase family is emerging as a crucial signaling molecule for a vast number of cellular functions including cell migration, proliferation, and differentiation. The function of p38 in myelination has only been recently addressed. Using pyridinyl imidazole-based p38 α/β selective inhibitors, we have reported a critical role for this kinase in the regulation of myelination, specifically, in controlling the differentiation of Schwann cells, and oligodendrocytes, the myelinating glia of the peripheral and central nervous systems, respectively. These compounds inhibited the accumulation of myelin-cell-specific markers, including myelin-specific glycosphingolipids, myelin-associated glycoprotein, and myelin basic protein. More significantly, myelination of dorsal root ganglia neurons by oligodendrocytes was irreversibly blocked by p38 inhibitors. Our current studies are focusing on the molecular mechanisms by which p38 regulates oligodendrocyte and Schwann cell differentiation and its role in models of myelination and remyelination.

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Abbreviations

Caspr:

Contactin associated protein

CGT:

UDP galactose:ceramide galactosyltransferase

CNP:

2′,3′-cyclic nucleotide 3′-phosphodiesterase

CNS:

central nervous system

DAPI:

4,6-diamidino-2-phenylindole dihydrochloride

DRG:

dorsal root ganglion

DRGN:

DRG neuron

ERK:

extracellular signal regulated kinase

FGF:

fibroblast growth factor

GalC:

galactosylceramide, galactocerebroside

HSP27:

heat shock protein 27

JNK:

c-jun N-terminal kinase

MAG:

myelin-associated glycoprotein

MAPK:

mitogen-activated protein kinase

MAPKAPK2/3:

MAPK activated protein kinase 2/3

MBP:

myelin basic protein

MNK:

MAPK-interacting kinase

MOBP:

myelin-associated oligodendrocyte basic protein

MSK:

mitogen- and stress-activated protein kinase

NGF:

nerve growth factor

NFH:

neurofilament heavy-chain

OLG:

oligodendrocyte

OLP:

oligodendrocyte progenitor

PDGF:

platelet-derived growth factor

PNS:

peripheral nervous system

SC:

Schwann cell

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Acknowledgements

Our work is funded by the Multiple Sclerosis Society of Canada (MSSC), and the Canadian Institutes of Health Research (CIHR). JDH and SH hold studentships from the MSSC.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, H3G 1Y6, Canada

    Jeffery D. Haines, Gabriela Fragoso, Shireen Hossain & Guillermina Almazan

  2. Department Biochemistry, McGill University, Montreal, QC, Canada

    Walter E. Mushynski

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  1. Jeffery D. Haines
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  2. Gabriela Fragoso
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  3. Shireen Hossain
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  4. Walter E. Mushynski
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  5. Guillermina Almazan
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Correspondence to Guillermina Almazan.

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Haines, J.D., Fragoso, G., Hossain, S. et al. p38 Mitogen-Activated Protein Kinase Regulates Myelination. J Mol Neurosci 35, 23–33 (2008). https://doi.org/10.1007/s12031-007-9011-0

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  • DOI: https://doi.org/10.1007/s12031-007-9011-0

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