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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 principales: Iridoy, Marina Oaia, Zubiri, Irene, Zelaya, María Victoria, Martinez, Leyre, Ausín, Karina, Lachen-Montes, Mercedes, Santamaría, Enrique, Fernandez-Irigoyen, Joaquín, Jericó, Ivonne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337647/
https://www.ncbi.nlm.nih.gov/pubmed/30577465
http://dx.doi.org/10.3390/ijms20010004
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author Iridoy, Marina Oaia
Zubiri, Irene
Zelaya, María Victoria
Martinez, Leyre
Ausín, Karina
Lachen-Montes, Mercedes
Santamaría, Enrique
Fernandez-Irigoyen, Joaquín
Jericó, Ivonne
author_facet Iridoy, Marina Oaia
Zubiri, Irene
Zelaya, María Victoria
Martinez, Leyre
Ausín, Karina
Lachen-Montes, Mercedes
Santamaría, Enrique
Fernandez-Irigoyen, Joaquín
Jericó, Ivonne
author_sort Iridoy, Marina Oaia
collection PubMed
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)).
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spelling pubmed-63376472019-01-22 Neuroanatomical Quantitative Proteomics Reveals Common Pathogenic Biological Routes between Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) Iridoy, Marina Oaia Zubiri, Irene Zelaya, María Victoria Martinez, Leyre Ausín, Karina Lachen-Montes, Mercedes Santamaría, Enrique Fernandez-Irigoyen, Joaquín Jericó, Ivonne Int J Mol Sci Article (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)). MDPI 2018-12-20 /pmc/articles/PMC6337647/ /pubmed/30577465 http://dx.doi.org/10.3390/ijms20010004 Text en © 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iridoy, Marina Oaia
Zubiri, Irene
Zelaya, María Victoria
Martinez, Leyre
Ausín, Karina
Lachen-Montes, Mercedes
Santamaría, Enrique
Fernandez-Irigoyen, Joaquín
Jericó, Ivonne
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)
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_short 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)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337647/
https://www.ncbi.nlm.nih.gov/pubmed/30577465
http://dx.doi.org/10.3390/ijms20010004
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