Neurology IV-Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", 20133 Milan, Italy.
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Department of Development and Stem Cells, CNRS UMR7104, INSERM U964, Université de Strasbourg, 67404 Illkirch CU Strasbourg, France.
Cells. 2019 Mar 23;8(3):279. doi: 10.3390/cells8030279.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. In ALS mice, neurodegeneration is associated with the proliferative restorative attempts of ependymal stem progenitor cells (epSPCs) that normally lie in a quiescent in the spinal cord. Thus, modulation of the proliferation of epSPCs may represent a potential strategy to counteract neurodegeneration. Recent studies demonstrated that FM19G11, a hypoxia-inducible factor modulator, induces epSPC self-renewal and proliferation. The aim of the study was to investigate whether FM19G11-loaded gold nanoparticles (NPs) can affect self-renewal and proliferation processes in epSPCs isolated from G93A-SOD1 mice at disease onset. We discovered elevated levels of SOX2, OCT4, AKT1, and AKT3, key genes associated with pluripotency, self-renewal, and proliferation, in G93A-SOD1 epSPCs at the transcriptional and protein levels after treatment with FM19G11-loaded NPs. We also observed an increase in the levels of the mitochondrial uncoupling protein () gene in treated cells. FM19G11-loaded NPs treatment also affected the expression of the cell cycle-related microRNA (miR)-19a, along with its target gene PTEN, in G93A-SOD1 epSPCs. Overall our findings establish the significant impact of FM19G11-loaded NPs on the cellular pathways involved in self-renewal and proliferation in G93A-SOD1 epSPCs, thus providing an impetus to the design of novel tailored approaches to delay ALS disease progression.
肌萎缩侧索硬化症（ALS）是一种影响运动神经元的进行性神经退行性疾病。在 ALS 小鼠中，神经退行性变与室管膜下干细胞祖细胞（epSPCs）的增殖修复尝试有关，epSPCs 通常在脊髓中处于静止状态。因此，调节 epSPCs 的增殖可能代表一种对抗神经退行性变的潜在策略。最近的研究表明，缺氧诱导因子调节剂 FM19G11 诱导 epSPC 自我更新和增殖。本研究旨在探讨 FM19G11 负载的金纳米颗粒（NPs）是否会影响疾病发作时从 G93A-SOD1 小鼠中分离出的 epSPCs 的自我更新和增殖过程。我们发现，在用 FM19G11 负载的 NPs 处理后，G93A-SOD1 epSPCs 在转录和蛋白水平上，与多能性、自我更新和增殖相关的关键基因 SOX2、OCT4、AKT1 和 AKT3 的水平升高。我们还观察到处理细胞中线粒体解偶联蛋白（）基因水平升高。FM19G11 负载的 NPs 处理还影响了 G93A-SOD1 epSPCs 中细胞周期相关 microRNA（miR）-19a 及其靶基因 PTEN 的表达。总的来说，我们的研究结果确立了 FM19G11 负载的 NPs 对 G93A-SOD1 epSPCs 中自我更新和增殖相关细胞通路的显著影响，为设计新型定制方法以延缓 ALS 疾病进展提供了动力。
