Journal article
Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment
D Matusica, F Alfonsi, BJ Turner, TJ Butler, SR Shepheard, ML Rogers, S Skeldal, CK Underwood, M Mangelsdorf, EJ Coulson
Journal of Cell Science | COMPANY OF BIOLOGISTS LTD | Published : 2016
DOI: 10.1242/jcs.173864
Abstract
The p75 neurotrophin receptor (p75NTR; 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 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..
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Awarded by National Health and Medical Research Council of Australia
Awarded by NuNerve Pty Ltd
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia [Career Development Fellowship 569601 and project grant 10012610 to E.J.C.]; the Australian Research Council; and NuNerve Pty Ltd [Linkage grant LP10012610 to E.J.C.]; Goodenough and Wantoks bequest (to E.J.C and M.M.); The Australian Government (Postgraduate Award to C.K.U); a Ross Maclean Fellowship (to M.M.); the Centre for Neuroscience, Flinders University and the Flinders Medical Centre Research Foundation (grants to D.M.); Australian Rotary Health (Neville & Jeanne York Motor Neuron Disease PhD Scholarship to S.R.S); and the Motor Neuron Disease Reseach Instititue of Australia (Rosalind Nicholson Grant to M-L.R.).