Abstract
Most scholars believe that amyloid-beta (Aβ) has the potential to induce apoptosis, stimulate an inflammatory cascade, promote oxidative stress and exacerbate the pathological progression of Alzheimer's disease (AD). Therefore, it is crucial to investigate the deposition of Aβ in AD. At approximately 6 months of age, APP/PS1 double transgenic mice gradually exhibit the development of plaques, as well as spatial and learning impairment. Notably, the hippocampus is specifically affected in the course of AD. Herein, 6-month-old APP/PS1 double transgenic mice were utilized, and the differentially expressed (DE) proteins in the hippocampus were identified and analyzed using 4D label-free quantitative proteomics technology and parallel reaction monitoring (PRM). Compared to wild-type mice, 29 proteins were upregulated and 25 proteins were downregulated in the AD group. Gene Ontology (GO) enrichment analysis of biological processes (BP) indicated that the DE proteins were mainly involved in ‘ribosomal large subunit biogenesis’. Molecular function (MF) analysis results were primarily associated with ‘5.8S rRNA binding’ and ‘structural constituent of ribosome’. In terms of cellular components (CC), the DE proteins were mainly found in ‘polysomal ribosome’, ‘cytosolic large ribosomal subunit’, ‘cytosolic ribosome’, and ‘large ribosomal subunit’, among others. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the results were mainly enriched in the ‘Ribosome signaling pathway’. The key target proteins identified were ribosomal protein (Rp)l18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6. The PRM verification results were consistent with the findings of the 4D label-free quantitative proteomics analysis. Overall, these findings suggest that Rpl18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6 may have potential therapeutic value for the treatment of AD by targeting Aβ.
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Data availability
All data used to support the findings of this study are included within the article.
Code availability
Not applicable.
Abbreviations
- AA-tRNA:
-
Aminoacyl-tRNA
- Aβ:
-
Amyloid-beta
- AD:
-
Alzheimer's disease
- AGC:
-
Automatic gain control
- APOE:
-
Apolipoprotein E
- APP:
-
Amyloid precursor protein
- BACE-1:
-
Beta-secretase 1
- BP:
-
Biological processes
- CC:
-
Cellular Component
- ChEIs:
-
Cholinesterase inhibitors
- DE:
-
Differentially expressed
- ELISA:
-
Enzyme linked immunosorbent assay
- FDA:
-
Food and Drug Administration
- FDR:
-
False-positive rate
- GFAP:
-
Glial fibrillary acid protein
- GO:
-
Gene Ontology
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- KOG:
-
EuKaryotic Orthologous Groups
- LC‒MS/MS:
-
Liquid chromatography-tandem mass spectrometry
- MF:
-
Molecular function
- MMSE:
-
Minimum Mental State Examination
- NFTs:
-
Neurofibrillary tangles
- PCA:
-
Principal components analysis
- PPI:
-
Protein‒protein interaction
- PRM:
-
Parallel reaction monitoring
- Rp:
-
Ribosomal protein
- RSD:
-
Relative standard deviation
- SP:
-
Senile plaques
- TCM:
-
Traditional Chinese medicine
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Funding
This study was supported by the Natural Science Foundation of Shandong (ZR2023QH159); the Education Department of Jilin Province ‘13th Five-Year’ Science and Technology Project (JJKH20200895KJ); the Science and Technology Ability Promotion Plan of Health Commission of Jilin Province (2019J058); the Jilin Provincial Science and Technology Department Key Research and Development-Medicine and Health Field (20200404065YY); and Traditional Chinese Medicine science and technology project of Shandong Province (Z-2023042).
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MQ, GC and JS designed the study. LN drafted the manuscript and edited and revised it critically for important intellectual content. LN and GJ contributed to the quality assessment, data analysis, and interpretation of the data. XT and QL carefully revised the manuscript. All authors contributed to the article and approved the submitted version.
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Feng, L., Wang, G., Song, Q. et al. Proteomics revealed an association between ribosome-associated proteins and amyloid beta deposition in Alzheimer's disease. Metab Brain Dis 39, 263–282 (2024). https://doi.org/10.1007/s11011-023-01330-3
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DOI: https://doi.org/10.1007/s11011-023-01330-3