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Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potenti...

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Autores principales: Lachén-Montes, Mercedes, Mendizuri, Naroa, Ausin, Karina, Andrés-Benito, Pol, Ferrer, Isidro, Fernández-Irigoyen, Joaquín, Santamaría, Enrique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664257/
https://www.ncbi.nlm.nih.gov/pubmed/33167591
http://dx.doi.org/10.3390/ijms21218311
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author Lachén-Montes, Mercedes
Mendizuri, Naroa
Ausin, Karina
Andrés-Benito, Pol
Ferrer, Isidro
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
author_facet Lachén-Montes, Mercedes
Mendizuri, Naroa
Ausin, Karina
Andrés-Benito, Pol
Ferrer, Isidro
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
author_sort Lachén-Montes, Mercedes
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potential non-motor finding in ALS, the pathobiochemistry at the olfactory level remains unknown. Here, we applied an olfactory quantitative proteotyping approach to analyze the magnitude of the olfactory bulb (OB) proteostatic imbalance in ALS subjects (n = 12) with respect to controls (n = 8). Around 3% of the quantified OB proteome was differentially expressed, pinpointing aberrant protein expression involved in vesicle-mediated transport, macroautophagy, axon development and gliogenesis in ALS subjects. The overproduction of olfactory marker protein (OMP) points out an imbalance in the olfactory signal transduction in ALS. Accompanying the specific overexpression of glial fibrillary acidic protein (GFAP) and Bcl-xL in the olfactory tract (OT), a tangled disruption of signaling routes was evidenced across the OB–OT axis in ALS. In particular, the OB survival signaling dynamics clearly differ between ALS and frontotemporal lobar degeneration (FTLD), two faces of TDP-43 proteinopathy. To the best of our knowledge, this is the first report on high-throughput molecular characterization of the olfactory proteostasis in ALS.
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spelling pubmed-76642572020-11-14 Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis Lachén-Montes, Mercedes Mendizuri, Naroa Ausin, Karina Andrés-Benito, Pol Ferrer, Isidro Fernández-Irigoyen, Joaquín Santamaría, Enrique Int J Mol Sci Article Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potential non-motor finding in ALS, the pathobiochemistry at the olfactory level remains unknown. Here, we applied an olfactory quantitative proteotyping approach to analyze the magnitude of the olfactory bulb (OB) proteostatic imbalance in ALS subjects (n = 12) with respect to controls (n = 8). Around 3% of the quantified OB proteome was differentially expressed, pinpointing aberrant protein expression involved in vesicle-mediated transport, macroautophagy, axon development and gliogenesis in ALS subjects. The overproduction of olfactory marker protein (OMP) points out an imbalance in the olfactory signal transduction in ALS. Accompanying the specific overexpression of glial fibrillary acidic protein (GFAP) and Bcl-xL in the olfactory tract (OT), a tangled disruption of signaling routes was evidenced across the OB–OT axis in ALS. In particular, the OB survival signaling dynamics clearly differ between ALS and frontotemporal lobar degeneration (FTLD), two faces of TDP-43 proteinopathy. To the best of our knowledge, this is the first report on high-throughput molecular characterization of the olfactory proteostasis in ALS. MDPI 2020-11-05 /pmc/articles/PMC7664257/ /pubmed/33167591 http://dx.doi.org/10.3390/ijms21218311 Text en © 2020 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
Lachén-Montes, Mercedes
Mendizuri, Naroa
Ausin, Karina
Andrés-Benito, Pol
Ferrer, Isidro
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
title Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
title_full Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
title_fullStr Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
title_full_unstemmed Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
title_short Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
title_sort amyotrophic lateral sclerosis is accompanied by protein derangements in the olfactory bulb-tract axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664257/
https://www.ncbi.nlm.nih.gov/pubmed/33167591
http://dx.doi.org/10.3390/ijms21218311
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