Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
Llanos-González, Emilio (Universidad de Castilla-La Mancha)
Sancho-Bielsa, Francisco J. (Universidad de Castilla-La Mancha)
Frontiñán-Rubio, Javier (Universidad de Castilla-La Mancha)
Rabanal-Ruíz, Yoana (Universidad de Castilla-La Mancha)
García-Carpintero, Sonia (Universidad de Castilla-La Mancha)
Chicano, Eduardo (Universidad de Córdoba)
Úbeda-Banon, Isabel (Universidad de Castilla-La Mancha)
Flores-Cuadrado, Alicia (Universidad de Castilla-La Mancha)
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona)
Alcaín, Francisco Javier (Universidad de Castilla-La Mancha)
Peinado, Juan Ramón (Universidad de Castilla-La Mancha)
Durán-Prado, Mario (Universidad de Castilla-La Mancha)

Date:	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.
Grants:	Agencia Estatal de Investigación PID2019-108659RB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	3xTg-AD mice ; Alzheimer's disease ; Coenzyme Q10 ; MALDI-imaging ; Mass spectrometry ; Ubiquinol
Published in:	Antioxidants, Vol. 12 (march 2023) , ISSN 2076-3921

DOI: 10.3390/antiox12030747
PMID: 36978996

14 p, 4.3 MB

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