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Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer’s disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiqui...

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Autores principales: Llanos-González, Emilio, Sancho-Bielsa, Francisco J., Frontiñán-Rubio, Javier, Rabanal-Ruíz, Yoana, García-Carpintero, Sonia, Chicano, Eduardo, Úbeda-Banon, Isabel, Flores-Cuadrado, Alicia, Giménez-Llort, Lydia, Alcaín, Francisco Javier, Peinado, Juan Ramón, Durán-Prado, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044705/
https://www.ncbi.nlm.nih.gov/pubmed/36978996
http://dx.doi.org/10.3390/antiox12030747
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author Llanos-González, Emilio
Sancho-Bielsa, Francisco J.
Frontiñán-Rubio, Javier
Rabanal-Ruíz, Yoana
García-Carpintero, Sonia
Chicano, Eduardo
Úbeda-Banon, Isabel
Flores-Cuadrado, Alicia
Giménez-Llort, Lydia
Alcaín, Francisco Javier
Peinado, Juan Ramón
Durán-Prado, Mario
author_facet Llanos-González, Emilio
Sancho-Bielsa, Francisco J.
Frontiñán-Rubio, Javier
Rabanal-Ruíz, Yoana
García-Carpintero, Sonia
Chicano, Eduardo
Úbeda-Banon, Isabel
Flores-Cuadrado, Alicia
Giménez-Llort, Lydia
Alcaín, Francisco Javier
Peinado, Juan Ramón
Durán-Prado, Mario
author_sort Llanos-González, Emilio
collection PubMed
description Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer’s disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI–MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model.
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spelling pubmed-100447052023-03-29 Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation Llanos-González, Emilio Sancho-Bielsa, Francisco J. Frontiñán-Rubio, Javier Rabanal-Ruíz, Yoana García-Carpintero, Sonia Chicano, Eduardo Úbeda-Banon, Isabel Flores-Cuadrado, Alicia Giménez-Llort, Lydia Alcaín, Francisco Javier Peinado, Juan Ramón Durán-Prado, Mario Antioxidants (Basel) Article Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer’s disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI–MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model. MDPI 2023-03-19 /pmc/articles/PMC10044705/ /pubmed/36978996 http://dx.doi.org/10.3390/antiox12030747 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Llanos-González, Emilio
Sancho-Bielsa, Francisco J.
Frontiñán-Rubio, Javier
Rabanal-Ruíz, Yoana
García-Carpintero, Sonia
Chicano, Eduardo
Úbeda-Banon, Isabel
Flores-Cuadrado, Alicia
Giménez-Llort, Lydia
Alcaín, Francisco Javier
Peinado, Juan Ramón
Durán-Prado, Mario
Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
title Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
title_full Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
title_fullStr Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
title_full_unstemmed Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
title_short Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
title_sort spatial and temporal protein modules signatures associated with alzheimer disease in 3xtg-ad mice are restored by early ubiquinol supplementation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044705/
https://www.ncbi.nlm.nih.gov/pubmed/36978996
http://dx.doi.org/10.3390/antiox12030747
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