Department of Neurology, the Second Affiliated Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China.
Department of Neurosurgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, Shandong, China.
Metab Brain Dis. 2024 Feb;39(2):263-282. doi: 10.1007/s11011-023-01330-3. Epub 2023 Nov 29.
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.
大多数学者认为淀粉样蛋白-β（Aβ）有诱导细胞凋亡、刺激炎症级联反应、促进氧化应激和加重阿尔茨海默病（AD）病理进展的潜力。因此，研究 Aβ在 AD 中的沉积至关重要。大约在 6 月龄时，APP/PS1 双转基因小鼠逐渐表现出斑块的形成以及空间和学习障碍。值得注意的是，AD 过程中特别影响海马体。在此，使用 6 月龄的 APP/PS1 双转基因小鼠，通过 4D 无标记定量蛋白质组学技术和平行反应监测（PRM），鉴定和分析海马体中的差异表达（DE）蛋白。与野生型小鼠相比，AD 组中有 29 个蛋白上调，25 个蛋白下调。生物过程（BP）的基因本体论（GO）富集分析表明，DE 蛋白主要参与“核糖体大亚基生物发生”。分子功能（MF）分析结果主要与“5.8S rRNA 结合”和“核糖体结构成分”相关。在细胞成分（CC）方面，DE 蛋白主要存在于“多核糖体”、“胞质大核糖体亚基”、“胞质核糖体”和“大亚基核糖体”等。此外，京都基因与基因组百科全书（KEGG）分析表明，结果主要富集在“核糖体信号通路”中。鉴定的关键靶蛋白为核糖体蛋白（Rp）l18、Rpl17、Rpl19、Rpl24、Rpl35 和 Rpl6。PRM 验证结果与 4D 无标记定量蛋白质组学分析结果一致。总之，这些发现表明，Rpl18、Rpl17、Rpl19、Rpl24、Rpl35 和 Rpl6 可能通过靶向 Aβ 具有治疗 AD 的潜在治疗价值。
