A small peptide mimetic of brain-derived neurotrophic factor promotes peripheral myelination
Article first published online: 24 FEB 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 125, Issue 3, pages 386–398, May 2013
How to Cite
J. Neurochem.(2013) 125, 386–398.
- Issue published online: 21 APR 2013
- Article first published online: 24 FEB 2013
- Accepted manuscript online: 25 JAN 2013 11:58AM EST
- Manuscript Revised: 22 JAN 2013
- Manuscript Accepted: 22 JAN 2013
- Manuscript Received: 8 NOV 2012
- BDNF ;
- Schwann cell
The expression of the neurotrophins and their receptors is essential for peripheral nervous system development and myelination. We have previously demonstrated that brain-derived neurotrophic factor (BDNF) exerts contrasting influences upon Schwann cell myelination in vitro – promoting myelination via neuronally expressed p75NTR, but inhibiting myelination via neuronally expressed TrkB. We have generated a small peptide called cyclo-dPAKKR that structurally mimics the region of BDNF that binds p75NTR. Here, we have investigated whether utilizing cyclo-dPAKKR to selectively target p75NTR is an approach that could exert a unified promyelinating response. Like BDNF, cyclo-dPAKKR promoted myelination of nerve growth factor-dependent neurons in vitro, an effect dependent on the neuronal expression of p75NTR. Importantly, cyclo-dPAKKR also significantly promoted the myelination of tropomyosin-related kinase receptor B-expressing neurons in vitro, whereas BDNF exerted a significant inhibitory effect. This indicated that while BDNF exerted a contrasting influence upon the myelination of distinct subsets of dorsal root ganglion (DRG) neurons in vitro, cyclo-dPAKKR uniformly promoted their myelination. Local injection of cyclo-dPAKKR adjacent to the developing sciatic nerve in vivo significantly enhanced myelin protein expression and significantly increased the number of myelinated axons. These results demonstrate that cyclo-dPAKKR promotes peripheral myelination in vitro and in vivo, suggesting it is a strategy worthy of further investigation for the treatment of peripheral demyelinating diseases.