Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)

(1) Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with an overlap in clinical presentation and neuropathology. Common and differential mechanisms leading to protein expression changes and neurodegeneration in ALS and FTD were studie...

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Autores: Iridoy Zulet, Marina, Zubiri, Irene, Zelaya Huerta, María Victoria, Martínez, Leire, Ausín, Karina, Lachén Montes, Mercedes, Santamaría Martínez, Enrique, Fernández Irigoyen, Joaquín, Jericó Pascual, Ivonne
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/34339
Acceso en línea:https://hdl.handle.net/2454/34339
Access Level:acceso abierto
Palabra clave:Amyotrophic lateral sclerosis (ALS)
Frontotemporal dementia (FTD)
Motor neuron
Proteomics
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spelling Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)Iridoy Zulet, MarinaZubiri, IreneZelaya Huerta, María VictoriaMartínez, LeireAusín, KarinaLachén Montes, MercedesSantamaría Martínez, EnriqueFernández Irigoyen, JoaquínJericó Pascual, IvonneAmyotrophic lateral sclerosis (ALS)Frontotemporal dementia (FTD)Motor neuronProteomics(1) Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with an overlap in clinical presentation and neuropathology. Common and differential mechanisms leading to protein expression changes and neurodegeneration in ALS and FTD were studied trough a deep neuroproteome mapping of the spinal cord. (2) Methods: A liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the spinal cord from ALS-TAR DNA-binding protein 43 (TDP-43) subjects, ubiquitin-positive frontotemporal lobar degeneration (FTLD-U) subjects and controls without neurodegenerative disease was performed. (3) Results: 281 differentially expressed proteins were detected among ALS versus controls, while 52 proteins were dysregulated among FTLD-U versus controls. Thirty-three differential proteins were shared between both syndromes. The resulting data was subjected to network-driven proteomics analysis, revealing mitochondrial dysfunction and metabolic impairment, both for ALS and FTLD-U that could be validated through the confirmation of expression levels changes of the Prohibitin (PHB) complex. (4) Conclusions: ALS-TDP-43 and FTLD-U share molecular and functional alterations, although part of the proteostatic impairment is region-and disease-specific. We have confirmed the involvement of specific proteins previously associated with ALS (Galectin 2 (LGALS3), Transthyretin (TTR), Protein S100-A6 (S100A6), and Protein S100-A11 (S100A11)) and have shown the involvement of proteins not previously described in the ALS context (Methanethiol oxidase (SELENBP1), Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1), Calcyclin-binding protein (CACYBP) and Rho-associated protein kinase 2 (ROCK2)). © 2018 by the authors. Licensee MDPI, Basel, Switzerland.This research is funded by the Navarre Association of ALS’s patients and relatives (ADELA-Navarra) and the Navarrabiomed-Miguel Servet Foundation, through “Ice Bucket Challenge” campaign donations. M.L.-M. was supported by a pre-doctoral fellowship from the Public University of Navarra (UPNA).MDPICiencias de la SaludOsasun ZientziakUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoa2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2454/34339reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglés© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/343392026-06-17T12:41:47Z
dc.title.none.fl_str_mv Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
title Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
spellingShingle Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
Iridoy Zulet, Marina
Amyotrophic lateral sclerosis (ALS)
Frontotemporal dementia (FTD)
Motor neuron
Proteomics
title_short Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
title_full Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
title_fullStr Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
title_full_unstemmed Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
title_sort Neuroanatomical quantitative proteomics reveals common pathogenic biological routes between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
dc.creator.none.fl_str_mv Iridoy Zulet, Marina
Zubiri, Irene
Zelaya Huerta, María Victoria
Martínez, Leire
Ausín, Karina
Lachén Montes, Mercedes
Santamaría Martínez, Enrique
Fernández Irigoyen, Joaquín
Jericó Pascual, Ivonne
author Iridoy Zulet, Marina
author_facet Iridoy Zulet, Marina
Zubiri, Irene
Zelaya Huerta, María Victoria
Martínez, Leire
Ausín, Karina
Lachén Montes, Mercedes
Santamaría Martínez, Enrique
Fernández Irigoyen, Joaquín
Jericó Pascual, Ivonne
author_role author
author2 Zubiri, Irene
Zelaya Huerta, María Victoria
Martínez, Leire
Ausín, Karina
Lachén Montes, Mercedes
Santamaría Martínez, Enrique
Fernández Irigoyen, Joaquín
Jericó Pascual, Ivonne
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
dc.subject.none.fl_str_mv Amyotrophic lateral sclerosis (ALS)
Frontotemporal dementia (FTD)
Motor neuron
Proteomics
topic Amyotrophic lateral sclerosis (ALS)
Frontotemporal dementia (FTD)
Motor neuron
Proteomics
description (1) Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with an overlap in clinical presentation and neuropathology. Common and differential mechanisms leading to protein expression changes and neurodegeneration in ALS and FTD were studied trough a deep neuroproteome mapping of the spinal cord. (2) Methods: A liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the spinal cord from ALS-TAR DNA-binding protein 43 (TDP-43) subjects, ubiquitin-positive frontotemporal lobar degeneration (FTLD-U) subjects and controls without neurodegenerative disease was performed. (3) Results: 281 differentially expressed proteins were detected among ALS versus controls, while 52 proteins were dysregulated among FTLD-U versus controls. Thirty-three differential proteins were shared between both syndromes. The resulting data was subjected to network-driven proteomics analysis, revealing mitochondrial dysfunction and metabolic impairment, both for ALS and FTLD-U that could be validated through the confirmation of expression levels changes of the Prohibitin (PHB) complex. (4) Conclusions: ALS-TDP-43 and FTLD-U share molecular and functional alterations, although part of the proteostatic impairment is region-and disease-specific. We have confirmed the involvement of specific proteins previously associated with ALS (Galectin 2 (LGALS3), Transthyretin (TTR), Protein S100-A6 (S100A6), and Protein S100-A11 (S100A11)) and have shown the involvement of proteins not previously described in the ALS context (Methanethiol oxidase (SELENBP1), Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1), Calcyclin-binding protein (CACYBP) and Rho-associated protein kinase 2 (ROCK2)). © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2454/34339
url https://hdl.handle.net/2454/34339
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
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repository.mail.fl_str_mv
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