PMID- 26503157
OWN - NLM
STAT- MEDLINE
DCOM- 20161026
LR  - 20170103
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 129
IP  - 3
DP  - 2016 Feb 1
TI  - Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin 
      receptor intracellular domain fragment.
PG  - 517-30
LID - 10.1242/jcs.173864 [doi]
AB  - The p75 neurotrophin receptor (p75(NTR); also known as NGFR) can mediate neuronal 
      apoptosis in disease or following trauma, and facilitate survival through 
      interactions with Trk receptors. Here we tested the ability of a p75(NTR)-derived 
      trophic cell-permeable peptide, c29, to inhibit p75(NTR)-mediated motor neuron 
      death. Acute c29 application to axotomized motor neuron axons decreased cell 
      death, and systemic c29 treatment of SOD1(G93A) mice, a common model of 
      amyotrophic lateral sclerosis, resulted in increased spinal motor neuron survival 
      mid-disease as well as delayed disease onset. Coincident with this, c29 treatment 
      of these mice reduced the production of p75(NTR) cleavage products. Although c29 
      treatment inhibited mature- and pro-nerve-growth-factor-induced death of cultured 
      motor neurons, and these ligands induced the cleavage of p75(NTR) in 
      motor-neuron-like NSC-34 cells, there was no direct effect of c29 on p75(NTR) 
      cleavage. Rather, c29 promoted motor neuron survival in vitro by enhancing the 
      activation of TrkB-dependent signaling pathways, provided that low levels of 
      brain-derived neurotrophic factor (BDNF) were present, an effect that was 
      replicated in vivo in SOD1(G93A) mice. We conclude that the c29 peptide 
      facilitates BDNF-dependent survival of motor neurons in vitro and in vivo.
CI  - (c) 2016. Published by The Company of Biologists Ltd.
FAU - Matusica, Dusan
AU  - Matusica D
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 
      4072, Australia Department of Anatomy & Histology, Centre for Neuroscience, 
      Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia.
FAU - Alfonsi, Fabienne
AU  - Alfonsi F
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 
      4072, Australia.
FAU - Turner, Bradley J
AU  - Turner BJ
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville 3052, Victoria 3051, Australia.
FAU - Butler, Tim J
AU  - Butler TJ
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 
      4072, Australia.
FAU - Shepheard, Stephanie R
AU  - Shepheard SR
AD  - Department of Human Physiology, Centre for Neuroscience, Flinders University, GPO 
      Box 2100, Adelaide, South Australia 5001, Australia.
FAU - Rogers, Mary-Louise
AU  - Rogers ML
AD  - Department of Human Physiology, Centre for Neuroscience, Flinders University, GPO 
      Box 2100, Adelaide, South Australia 5001, Australia.
FAU - Skeldal, Sune
AU  - Skeldal S
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 
      4072, Australia.
FAU - Underwood, Clare K
AU  - Underwood CK
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 
      4072, Australia.
FAU - Mangelsdorf, Marie
AU  - Mangelsdorf M
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 
      4072, Australia.
FAU - Coulson, Elizabeth J
AU  - Coulson EJ
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 
      4072, Australia e.coulson@uq.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151026
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell-Penetrating Peptides)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - EC 1.15.1.1 (SOD1 G93A protein)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Death/*physiology
MH  - Cell Survival/physiology
MH  - Cell-Penetrating Peptides/*metabolism
MH  - Cells, Cultured
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Motor Neurons/*metabolism
MH  - Receptor, Nerve Growth Factor/*metabolism
MH  - Signal Transduction/physiology
MH  - Spinal Cord/metabolism/physiology
MH  - Superoxide Dismutase/metabolism
OTO - NOTNLM
OT  - ALS
OT  - BDNF
OT  - Motor neuron
OT  - NGFR
OT  - Survival
OT  - TrkB
OT  - p75NTR
EDAT- 2015/10/28 06:00
MHDA- 2016/10/27 06:00
CRDT- 2015/10/28 06:00
PHST- 2015/05/04 00:00 [received]
PHST- 2015/10/22 00:00 [accepted]
PHST- 2015/10/28 06:00 [entrez]
PHST- 2015/10/28 06:00 [pubmed]
PHST- 2016/10/27 06:00 [medline]
AID - jcs.173864 [pii]
AID - 10.1242/jcs.173864 [doi]
PST - ppublish
SO  - J Cell Sci. 2016 Feb 1;129(3):517-30. doi: 10.1242/jcs.173864. Epub 2015 Oct 26.