Journal of Molecular Neuroscience

, Volume 35, Issue 1, pp 23–33

p38 Mitogen-Activated Protein Kinase Regulates Myelination

  • Jeffery D. Haines
  • Gabriela Fragoso
  • Shireen Hossain
  • Walter E. Mushynski
  • Guillermina Almazan
Article

DOI: 10.1007/s12031-007-9011-0

Cite this article as:
Haines, J.D., Fragoso, G., Hossain, S. et al. J Mol Neurosci (2008) 35: 23. doi:10.1007/s12031-007-9011-0

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.

Keywords

Differentiation Myelin p38 MAPK Oligodendrocyte Dorsal root ganglion neuron Schwann cell 

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

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Jeffery D. Haines
    • 1
  • Gabriela Fragoso
    • 1
  • Shireen Hossain
    • 1
  • Walter E. Mushynski
    • 2
  • Guillermina Almazan
    • 1
  1. 1.Department of Pharmacology and TherapeuticsMcGill UniversityMontrealCanada
  2. 2.Department BiochemistryMcGill UniversityMontrealCanada

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