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BMC Neurosci. 2008 Sep 9;9:83. doi: 10.1186/1471-2202-9-83.

MMP-28 as a regulator of myelination.

Author information

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

Abstract

BACKGROUND:

Matrix metalloproteinase-28 (MMP-28) is a poorly understood member of the matrix metalloproteinase family. Metalloproteinases are important mediators in the development of the nervous system and can contribute to the maturation of the neural micro-environment.

RESULTS:

MMP-28 added to myelinating rat dorsal root ganglion (DRG) co-cultures reduces myelination and two antibodies targeted to MMP-28 (pAb180 and pAb183) are capable of binding MMP-28 and inhibiting its activity in a dose-dependent manner. Addition of 30 nM pAb180 or pAb183 to rat DRG cultures resulted in the 2.6 and 4.8 fold enhancement of myelination respectively while addition of MMP-28 to DRG co-cultures resulted in enhanced MAPK, ErbB2 and ErbB3 phosphorylation. MMP-28 protein expression was increased within demyelinated lesions of mouse experimental autoimmune encephalitis (EAE) and human multiple sclerosis lesions compared to surrounding normal tissue.

CONCLUSION:

MMP-28 is upregulated in conditions of demyelination in vivo, induces signaling in vitro consistent with myelination inhibition and, neutralization of MMP-28 activity can enhance myelination in vitro. These results suggest inhibition of MMP-28 may be beneficial under conditions of dysmyelination.

PMID:
18778487
PMCID:
PMC2551619
DOI:
10.1186/1471-2202-9-83
[Indexed for MEDLINE]
Free PMC Article

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