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

Authors :
Emilio Llanos-González
Francisco J. Sancho-Bielsa
Javier Frontiñán-Rubio
Yoana Rabanal-Ruíz
Sonia García-Carpintero
Eduardo Chicano
Isabel Úbeda-Banon
Alicia Flores-Cuadrado
Lydia Giménez-Llort
Francisco Javier Alcaín
Juan Ramón Peinado
Mario Durán-Prado
Source :
Antioxidants, Vol 12, Iss 3, p 747 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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.

Details

Language :
English
ISSN :
20763921
Volume :
12
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Antioxidants
Publication Type :
Academic Journal
Accession number :
edsdoj.5e9afe27b74e480e8c3e4841c1e0ff83
Document Type :
article
Full Text :
https://doi.org/10.3390/antiox12030747