Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

Matusica, Dusan, Alfonsi, Fabienne, Turner, Bradley J., Butler, Tim J., Shepheard, Stephanie R., Rogers, Mary-Louise, Skeldal, Sune, Underwood, Clare K., Mangelsdorf, Marie and Coulson, Elizabeth J. (2016) Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment. Journal of Cell Science, 129 3: 517-530. doi:10.1242/jcs.173864

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Author Matusica, Dusan
Alfonsi, Fabienne
Turner, Bradley J.
Butler, Tim J.
Shepheard, Stephanie R.
Rogers, Mary-Louise
Skeldal, Sune
Underwood, Clare K.
Mangelsdorf, Marie
Coulson, Elizabeth J.
Title Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment
Formatted title
Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
1477-9137
Publication date 2016
Sub-type Article (original research)
DOI 10.1242/jcs.173864
Open Access Status File (Publisher version)
Volume 129
Issue 3
Start page 517
End page 530
Total pages 14
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Collection year 2017
Language eng
Formatted abstract
The neurotrophin receptor (p75NTR) can mediate neuronal apoptosis in disease or following trauma, and facilitate survival through interactions with Trk receptors. Here we tested the ability of a p75NTR-derived trophic cell-permeable peptide, c29, to inhibit p75NTR-mediated motor neuron death. Acute c29 application to axotomized motor neuron axons decreased cell death, and systemic c29 treatment of SOD1G93A 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 p75NTR 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 p75NTR in motor-neuron-like NSC-34 cells, there was no direct effect of c29 on p75NTR cleavage. Rather, c29 promoted motor neuron survival in vitro by enhancing the activation of TrkB-dependent signaling pathways, provided that low levels of BDNF were present, an effect that was replicated in vivo in SOD1G93A mice. We conclude that the c29 peptide facilitates BDNF-dependent survival of motor neurons in vitro and in vivo.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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Created: Wed, 09 Dec 2015, 11:48:31 EST by Susan Day on behalf of Queensland Brain Institute