Matrix metalloproteinase-2 is involved in myelination of dorsal root ganglia neurons

Helmar C. Lehmann, Angelika Köhne, Fabian Bernal, Parastoo Jangouk, G. M Z Hörste, Thomas Dehmel, Hans Peter Hartung, Stefano C. Previtali, Bernd C. Kieseier

Research output: Contribution to journalArticle

Abstract

Matrix metalloproteinases (MMPs) comprise a large family of endopeptidases that are capable of degrading all extracellular matrix components. There is increasing evidence that MMPs are not only involved in tissue destruction but may also exert beneficial effects during axonal regeneration and nerve remyelination. Here, we provide evidence that MMP-2 (gelatinase A) is associated with the physiological process of myelination in the peripheral nervous system (PNS). In a myelinating co-culture model of Schwann cells and dorsal root ganglia neurons, MMP-2 expression correlated with the degree of myelination as determined by immunocytochemistry, zymography, and immunosorbent assay. Modulation of MMP-2 activity by chemical inhibitors led to incomplete and aberrant myelin formation. In vivo MMP-2 expression was detected in the cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome as well as in CSF and sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy. Our findings suggest an important, previously unrecognized role for MMP-2 during myelination in the PNS. Endogenous or exogenous modulation of MMP-2 activity may be a relevant target to enhance regeneration in demyelinating diseases of the PNS.

Original languageEnglish
Pages (from-to)479-489
Number of pages11
JournalGLIA
Volume57
Issue number5
DOIs
Publication statusPublished - 2009

Keywords

  • Guillain-Barré syndrome
  • Immune-mediated neuropathy
  • Inflammation
  • Peripheral nerve
  • Regeneration
  • Schwann cell

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

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    Lehmann, H. C., Köhne, A., Bernal, F., Jangouk, P., Hörste, G. M. Z., Dehmel, T., Hartung, H. P., Previtali, S. C., & Kieseier, B. C. (2009). Matrix metalloproteinase-2 is involved in myelination of dorsal root ganglia neurons. GLIA, 57(5), 479-489. https://doi.org/10.1002/glia.20774