Gu Wenyu, Cong Xinli, Pei Yechun, Che Ajuyo Nuela Manka'a, Min Yi, Wang Dayong
Key Laboratory of Tropical Bioresources of the Educational Ministry of China, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.
Laboratory of Biopharmaceuticals and Molecular Pharmacology, One Health Cooperative Innovation Center, Hainan University, Haikou 570228, China.
Metabolites. 2024 Jun 29;14(7):369. doi: 10.3390/metabo14070369.
Alzheimer's disease (AD) is a neurodegenerative disease. Mitochondrial energy metabolism and p70 ribosomal protein S6 kinase (p70S6K) play significant roles in AD pathology. However, the potential relationship between them is unclear. In this study, bioinformatics methods were initially applied to analyze the transcriptomic data in the CA1 and the primary visual cortex of patients with AD and Aβ42-treated SH-SY5Y cells. By applying secreted Aβ42 and gene silencing in cells, we explored disorders in mitochondrial function and the regulatory roles of p70S6K by flow cytometry, laser scanning confocal microscopy, high-performance liquid chromatography, Western blotting, and quantitative reverse transcription PCR. The study reveals that impaired mitochondrial energy metabolism is a potential pathological feature of AD and that gene silencing reversed most of the changes induced by Aβ42, such as the activities of the electron transport chain complexes I and III, as well as ATP synthase, ATP production, generation of reactive oxygen species, mitochondrial membrane potential, and phosphorylation of AMPK, PINK1, and Parkin, all of which are required for mitochondria to function properly in the cell.
阿尔茨海默病（AD）是一种神经退行性疾病。线粒体能量代谢和p70核糖体蛋白S6激酶（p70S6K）在AD病理学中起重要作用。然而，它们之间的潜在关系尚不清楚。在本研究中，最初应用生物信息学方法分析AD患者海马CA1区和初级视皮层以及经Aβ42处理的SH-SY5Y细胞中的转录组数据。通过在细胞中应用分泌型Aβ42和基因沉默，我们利用流式细胞术、激光扫描共聚焦显微镜、高效液相色谱、蛋白质免疫印迹法和定量逆转录PCR探索了线粒体功能障碍以及p70S6K的调节作用。该研究表明，线粒体能量代谢受损是AD的潜在病理特征，并且基因沉默逆转了Aβ42诱导的大多数变化，如电子传递链复合物I和III以及ATP合酶的活性、ATP产生、活性氧生成、线粒体膜电位以及AMPK、PINK1和Parkin的磷酸化，所有这些都是线粒体在细胞中正常发挥功能所必需的。
