PMID- 25461619
OWN - NLM
STAT- MEDLINE
DCOM- 20150709
LR  - 20150112
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 63
DP  - 2014 Nov
TI  - TDP6, a brain-derived neurotrophic factor-based trkB peptide mimetic, promotes 
      oligodendrocyte myelination.
PG  - 132-40
AB  - Brain-derived neurotrophic factor (BDNF) plays critical roles in the development 
      and maintenance of the central (CNS) and peripheral nervous systems (PNS). BDNF 
      exerts its biological effects via tropomyosin-related kinase B (TrkB) and the p75 
      neurotrophin receptor (p75NTR). We have recently identified that BDNF promotes 
      CNS myelination via oligodendroglial TrkB receptors. In order to selectively 
      target TrkB to promote CNS myelination, we have used a putative TrkB agonist, a 
      small multicyclic peptide (tricyclic dimeric peptide 6, TDP6) previously 
      described by us that structurally mimics a region of BDNF that binds TrkB. We 
      confirmed that TDP6 acts as a TrkB agonist as it provoked autophosphorylation of 
      TrkB and its downstream signalling effector extracellular related-kinase 1 and 2 
      (Erk1/2) in primary oligodendrocytes. Using an in vitro myelination assay, we 
      show that TDP6 significantly promotes myelination by oligodendrocytes in vitro, 
      as evidenced by enhanced myelin protein expression and an increased number of 
      myelinated axonal segments. In contrast, a second, structurally distinct BDNF 
      mimetic (cyclo-dPAKKR) that targets p75NTR had no effect upon oligodendrocyte 
      myelination in vitro, despite the fact that cyclo-dPAKKR is a very effective 
      promoter of peripheral (Schwann cell) myelination. The selectivity of TDP6 was 
      further verified by using TrkB-deficient oligodendrocytes, in which TDP6 failed 
      to promote myelination, indicating that the pro-myelinating effect of TDP6 is 
      oligodendroglial TrkB-dependent. Together, our results demonstrate that TDP6 is a 
      novel BDNF mimetic that promotes oligodendrocyte myelination in vitro via 
      targeting TrkB.
FAU - Wong, Agnes W
AU  - Wong AW
FAU - Giuffrida, Lauren
AU  - Giuffrida L
FAU - Wood, Rhiannon
AU  - Wood R
FAU - Peckham, Haley
AU  - Peckham H
FAU - Gonsalvez, David
AU  - Gonsalvez D
FAU - Murray, Simon S
AU  - Murray SS
FAU - Hughes, Richard A
AU  - Hughes RA
FAU - Xiao, Junhua
AU  - Xiao J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Peptidomimetics)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/chemistry
MH  - Cells, Cultured
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelin Sheath/genetics/*metabolism
MH  - Oligodendroglia/*drug effects/metabolism
MH  - Peptidomimetics/*pharmacology
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/*agonists/metabolism
EDAT- 2014/12/03 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/08/11 00:00 [received]
PHST- 2014/10/09 00:00 [revised]
PHST- 2014/10/15 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - S1044-7431(14)00167-5 [pii]
AID - 10.1016/j.mcn.2014.10.002 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2014 Nov;63:132-40. doi: 10.1016/j.mcn.2014.10.002.