PMID- 23350698
OWN - NLM
STAT- MEDLINE
DCOM- 20130620
LR  - 20231213
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 125
IP  - 3
DP  - 2013 May
TI  - A small peptide mimetic of brain-derived neurotrophic factor promotes peripheral 
      myelination.
PG  - 386-98
LID - 10.1111/jnc.12168 [doi]
AB  - 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.
CI  - (c) 2013 International Society for Neurochemistry.
FAU - Xiao, Junhua
AU  - Xiao J
AD  - Department of Anatomy and Neuroscience, The University of Melbourne, Victoria, 
      Australia. xiaoj@unimelb.edu.au
FAU - Hughes, Richard A
AU  - Hughes RA
FAU - Lim, Joe Y
AU  - Lim JY
FAU - Wong, Agnes W
AU  - Wong AW
FAU - Ivanusic, Jason J
AU  - Ivanusic JJ
FAU - Ferner, Anita H
AU  - Ferner AH
FAU - Kilpatrick, Trevor J
AU  - Kilpatrick TJ
FAU - Murray, Simon S
AU  - Murray SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130224
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuregulins)
RN  - 0 (Nrg3 protein, mouse)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Ngfr protein, mouse)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*chemistry/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dose-Response Relationship, Drug
MH  - Ganglia, Spinal/cytology
MH  - Gene Expression Regulation, Developmental/drug effects/genetics
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myelin Sheath/drug effects/*metabolism
MH  - Neuregulins
MH  - Neurons/drug effects/metabolism
MH  - Peptides/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Nerve Growth Factor/deficiency
MH  - Schwann Cells
MH  - Sciatic Nerve/drug effects/*metabolism
EDAT- 2013/01/29 06:00
MHDA- 2013/06/21 06:00
CRDT- 2013/01/29 06:00
PHST- 2012/11/08 00:00 [received]
PHST- 2013/01/22 00:00 [revised]
PHST- 2013/01/22 00:00 [accepted]
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/06/21 06:00 [medline]
AID - 10.1111/jnc.12168 [doi]
PST - ppublish
SO  - J Neurochem. 2013 May;125(3):386-98. doi: 10.1111/jnc.12168. Epub 2013 Feb 24.