3b06f0027b0104f20c1ca25b390873c9 pmc_10044705.pdf 43b572e28e47765164a0019fb9684792603b1724 pmc_10044705.pdf fbfd8f0599552c6bf57eef99b535024c84bbf563ce09792b209d83a3da3d2959 pmc_10044705.pdf Title: Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation Subject: 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. Keywords: 3xTg-AD mice; Alzheimer’s disease; coenzyme Q10; MALDI-imaging; mass spectrometry; ubiquinol Author: 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 and Mario Durán-Prado Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sun Mar 19 08:28:48 2023 CET ModDate: Sun Mar 19 08:32:59 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4522444 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- REOBYA+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 AVTQTB+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 SNSFSJ+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 ADETIZ+VnURWPalladioL Type 1 Custom yes yes no 23 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 28 0 HNMBQN+VnURWPalladioL-Bold Type 1 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Children: Item: Title: Behavioural Tests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: MALDI MSI Methodology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Functional Analysis and Protein Protein Interaction Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Protein Modules Validation by Immunofluorescence Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Info: Title: Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation Author: 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 and Mario Durán-Prado Subject: 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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