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Network-based proteomic approaches reveal the neurodegenerative, neuroprotective and pain-related mechanisms involved after retrograde axonal damage

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dc.contributor.author Casas, Caty
dc.contributor.author Isús Díaz, Laura, 1989-
dc.contributor.author Herrando Grabulosa, Mireia
dc.contributor.author Mancuso, Francesco M.
dc.contributor.author Borrás, Eva
dc.contributor.author Sabidó Aguadé, Eduard, 1981-
dc.contributor.author Forés, Joaquim
dc.contributor.author Aloy, Patrick, 1972-
dc.date.accessioned 2015-11-20T19:05:23Z
dc.date.available 2015-11-20T19:05:23Z
dc.date.issued 2015
dc.identifier.citation Casas C, Isus L, Herrando-Grabulosa M, Mancuso FM, Borrás E, Sabidó E et al. Network-based proteomic approaches reveal the neurodegenerative, neuroprotective and pain-related mechanisms involved after retrograde axonal damage. Sci Rep. 2015;5:9185. DOI: 10.1038/srep09185
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/25174
dc.description.abstract Neurodegenerative processes are preceded by neuronal dysfunction and synaptic disconnection. Disconnection between spinal motoneuron (MN) soma and synaptic target leads either to a retrograde degenerative process or to a regenerative reaction, depending injury proximity among other factors. Distinguished key events associated with one or other processes may give some clues towards new therapeutical approaches based on boosting endogenous neuroprotective mechanisms. Root mechanical traction leads to retrograde MN degeneration, but share common initial molecular mechanisms with a regenerative process triggered by distal axotomy and suture. By 7 days post-injury, key molecular events starts to diverge and sign apart each destiny. We used comparative unbiased proteomics to define these signatures, coupled to a novel network-based analysis to get biological meaning. The procedure implicated the previous generation of combined topological information from manual curated 19 associated biological processes to be contrasted with the proteomic list using gene enrichment analysis tools. The novel and unexpected results suggested that motoneurodegeneration is better explained mainly by the concomitant triggering of anoikis, anti-apoptotic and neuropathic-pain related programs. In contrast, the endogenous neuroprotective mechanisms engaged after distal axotomy included specifically rather anti-anoikis and selective autophagy. Validated protein-nodes and processes are highlighted across discussion.
dc.description.sponsorship This work was supported by grants from Fundació La marató-TV3 (#110432) who was funding all the present work and the postdoctoral fellowship of MHG. This work was partially supported by the European commission through the SyStemAge project (Agreement no: 306240). LI is a recipient of a PhD La Caixa fellowship.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Scientific reports. 2015;5:9185
dc.rights © This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Neurogenètica
dc.subject.other Proteïnes
dc.title Network-based proteomic approaches reveal the neurodegenerative, neuroprotective and pain-related mechanisms involved after retrograde axonal damage
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/srep09185
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/306240
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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