Journal
JOURNAL OF NEUROCHEMISTRY
Volume 124, Issue 1, Pages 36-44Publisher
WILEY-BLACKWELL
DOI: 10.1111/jnc.12062
Keywords
autophagy; C-terminal domain of tetanus toxin; ERK1; 2; glutamate excitotoxicity; GSK3 ss; motoneurons spinal cord organotypic cultures
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Funding
- Ministerio de Ciencia e Innovacion of Spain [SAF2009-13626, SAF2006-15184]
- Instituto de Salud Carlos III through funds of Red de Terapia Celular (TERCEL) of Spain
- Ministerio de Educacion y Ciencia of Spain
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The C-terminal domain of tetanus toxin (Hc-TeTx) has been suggested to act as a neuroprotective agent by activating signaling pathways related to neurotrophins and also to exert anti-apoptotic effects. Here, we show the beneficial properties of the recombinant protein Hc-TeTx to protect spinal motoneurons against excitotoxic damage. In vitro spinal cord organotypic cultures were used to assess acute glutamate excitotoxic damage. Our results indicate that Hc-TeTx treatment improves motoneuron survival within a short therapeutical window (the first 2 h post-injury). Within this interval, we found that p44/p42 MAP kinase (ERK1/2) and glycogen synthase kinase-3 (GSK3 beta) signaling pathways play a crucial role in the neuroprotective effect. Moreover, we demonstrated that HcTeTx treatment initiate autophagy which is ERK1/2- and GSK3 beta-dependent. These findings suggest a possible therapeutical tool to improve motoneuron survival immediately after excitotoxic insults or during the secondary injury phase that occurs after spinal cord trauma.
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