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Network-based proteomic approaches reveal the neurodegenerative, neuroprotective and pain-related mechanisms involved after retrograde axonal damage
Casas Louzao, Caty (Universitat Autònoma de Barcelona. Institut de Neurociències)
Isus, Laura (Institut de Recerca Biomèdica)
Herrando-Grabulosa, Mireia (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Mancuso, Francesco M. (Vall d'Hebron Institut d'Oncologia)
Borrás, Eva (Universitat Pompeu Fabra. Centre de Regulació Genòmica)
Sabidó, Eduardo (Universitat Pompeu Fabra. Centre de Regulació Genòmica)
Forés Vineta, Joaquim (Universitat de Barcelona. Hospital Clínic)
Aloy, Patrick (Institució Catalana de Recerca i Estudis Avançats (ICREA))

Date: 2015
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.
Note: We thank to Ghyzlane El Korchi for excellent technical help and to Marta Morell for taking tremendous good care of the animals. 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.
Note: Altres ajuts: Fundació La marató-TV3 (ajut núm. 110432)
Note: Número d'acord de subvenció European Commission/306240
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Animals ; Anoikis ; Axons ; Axotomy ; Male ; Motor Neurons ; Neurodegenerative Diseases ; Pain ; Protein Interaction Maps ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Retrograde Degeneration
Published in: Scientific reports, Vol. 5 (2015) , art. 9185, ISSN 2045-2322

DOI: 10.1038/srep09185
PMID: 25784190


13 p, 3.4 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2019-04-11, last modified 2019-11-06



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