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MMP-28 as a regulator of myelination

Sean R Werner1, Joseph E Dotzlaf, Rosamund C Smith

  • 1Biotechnology Discovery Research, Lilly Corporate Center, Indianapolis, IN 46225, USA. sean.werner@sbcglobal.net

BMC Neuroscience
|September 10, 2008
PubMed
Abstract

Insights

Matrix metalloproteinase-28 (MMP-28) inhibits myelination. Neutralizing MMP-28 enhances myelination in vitro and suggests its inhibition may benefit demyelination conditions.

Area of Science:

  • Neuroscience
  • Biochemistry

Background:

  • Matrix metalloproteinase-28 (MMP-28) is a poorly understood enzyme.
  • Metalloproteinases play roles in nervous system development and neural micro-environment maturation.

Purpose of the Study:

  • To investigate the role of MMP-28 in myelination.
  • To determine if MMP-28 inhibition can enhance myelination.

Main Methods:

  • MMP-28 was added to myelinating rat dorsal root ganglion (DRG) co-cultures.
  • Antibodies targeting MMP-28 were used to inhibit its activity.
  • MMP-28 expression was analyzed in demyelinated lesions.

Main Results:

  • MMP-28 addition reduced myelination and increased MAPK, ErbB2, and ErbB3 phosphorylation.
  • Antibodies against MMP-28 dose-dependently enhanced myelination.
  • MMP-28 was upregulated in demyelinated lesions of EAE mice and human multiple sclerosis.

Conclusions:

  • MMP-28 is upregulated in demyelination and inhibits myelination in vitro.
  • Neutralizing MMP-28 activity enhances myelination.
  • Inhibiting MMP-28 may be a therapeutic strategy for dysmyelination disorders.

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