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An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.

Publication ,  Journal Article
Li, F-Q; Fowler, KA; Neil, JE; Colton, CA; Vitek, MP
Published in: J Pharmacol Exp Ther
July 2010

Elevated apolipoprotein E (apoE) synthesis within crushed sciatic nerves advocates that apoE could benefit axonal repair and reconstruction of axonal and myelin membranes. We created an apoE-mimetic peptide, COG112 (acetyl-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRLL-amide), and found that postinjury treatment with COG112 significantly improved recovery of motor and sensory function following sciatic nerve crush in C57BL/6 mice. Morphometric analysis of injured sciatic nerves revealed that COG112 promoted axonal regrowth after 2 weeks of treatment. More strikingly, the thickness of myelin sheaths was increased by COG112 treatment. Consistent with these histological findings, COG112 potently elevated growth associated protein 43 (GAP-43) and peripheral myelin protein zero (P0), which are markers of axon regeneration and remyelination, respectively. Electron microscopic examination further suggested that the apoE-mimetic COG112 may increase clearance of myelin debris. Schwann cell uptake of cholesterol-containing low-density lipoprotein particles was selectively enhanced by COG112 treatment in a Schwann cell line S16. Moreover, COG112 significantly promoted axon elongation in primary dorsal root ganglion cultures from rat pups. Considering that cholesterol and lipids are needed for reconstructing myelin sheaths and axon extension, these data support a hypothesis where supplementation with exogenous apoE-mimetics such as COG112 may be a promising strategy for restoring lost functional and structural elements following nerve injury.

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Published In

J Pharmacol Exp Ther

DOI

EISSN

1521-0103

Publication Date

July 2010

Volume

334

Issue

1

Start / End Page

106 / 115

Location

United States

Related Subject Headings

  • Walking
  • Treatment Outcome
  • Sciatic Neuropathy
  • Sciatic Nerve
  • Schwann Cells
  • Rats
  • Pharmacology & Pharmacy
  • Peptides
  • Nerve Regeneration
  • Nerve Fibers, Myelinated
 

Citation

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Li, F.-Q., Fowler, K. A., Neil, J. E., Colton, C. A., & Vitek, M. P. (2010). An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury. J Pharmacol Exp Ther, 334(1), 106–115. https://doi.org/10.1124/jpet.110.167882
Li, Feng-Qiao, Kenneth A. Fowler, Jessica E. Neil, Carol A. Colton, and Michael P. Vitek. “An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.J Pharmacol Exp Ther 334, no. 1 (July 2010): 106–15. https://doi.org/10.1124/jpet.110.167882.
Li F-Q, Fowler KA, Neil JE, Colton CA, Vitek MP. An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury. J Pharmacol Exp Ther. 2010 Jul;334(1):106–15.
Li, Feng-Qiao, et al. “An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.J Pharmacol Exp Ther, vol. 334, no. 1, July 2010, pp. 106–15. Pubmed, doi:10.1124/jpet.110.167882.
Li F-Q, Fowler KA, Neil JE, Colton CA, Vitek MP. An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury. J Pharmacol Exp Ther. 2010 Jul;334(1):106–115.
Journal cover image

Published In

J Pharmacol Exp Ther

DOI

EISSN

1521-0103

Publication Date

July 2010

Volume

334

Issue

1

Start / End Page

106 / 115

Location

United States

Related Subject Headings

  • Walking
  • Treatment Outcome
  • Sciatic Neuropathy
  • Sciatic Nerve
  • Schwann Cells
  • Rats
  • Pharmacology & Pharmacy
  • Peptides
  • Nerve Regeneration
  • Nerve Fibers, Myelinated