Bruno Francesca, Naselli Flores, Brancato Desiree, Volpes Sara, Cardinale Paola Sofia, Saccone Salvatore, Federico Concetta, Caradonna Fabio
Department Biological, Geological, and Environmental Sciences, University of Catania, 95124 Catania, Italy.
Department Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90133 Palermo, Italy.
Nutrients. 2024 Nov 29;16(23):4152. doi: 10.3390/nu16234152.
The "Cell Cycle Hypothesis" suggests that the abnormal re-entry of neurons into the cell division cycle leads to neurodegeneration, a mechanism supported by in vitro studies on neuronal-like cells treated with the hyperphosphorylating agent forskolin. Pterostilbene, a bioavailable compound found in foods such as blueberries and grapes, may exert neuroprotective effects and could serve as a potential adjunct therapy for neurodegenerative diseases. . In this study, we investigated the effects of pterostilbene on neuronal-like cells derived from the human neuroblastoma SK-N-BE cell line, where cell cycle reactivation was induced by forskolin treatment. We analyzed molecular endpoints associated with differentiated versus replicative cell states, specifically the following: (a) the expression of cyclin , (b) the Ki67 cell proliferation marker, (c) the AT8 nuclear tau epitope, and (d) genome-wide DNA methylation changes. . Our findings indicate that pterostilbene exerts distinct effects on the cell division cycle depending on the cellular state, with neuroprotective benefits observed in differentiated neuronal-like cells, but not in cells undergoing induced division. Additionally, pterostilbene alters DNA methylation patterns. These results suggest that pterostilbene may offer neuroprotective advantages for differentiated neuronal-like cells. However, further studies are required to confirm these effects in vivo by examining specific biomarkers in human populations consuming pterostilbene-containing foods.
“细胞周期假说”认为，神经元异常重新进入细胞分裂周期会导致神经退行性变，这一机制得到了用超磷酸化剂福司可林处理的类神经元细胞的体外研究支持。紫檀芪是一种在蓝莓和葡萄等食物中发现的具有生物利用度的化合物，可能具有神经保护作用，并可作为神经退行性疾病的一种潜在辅助治疗方法。在本研究中，我们研究了紫檀芪对源自人神经母细胞瘤SK-N-BE细胞系的类神经元细胞的影响，其中细胞周期重新激活是通过福司可林处理诱导的。我们分析了与分化细胞状态和复制细胞状态相关的分子终点，具体如下：（a）细胞周期蛋白的表达，（b）Ki67细胞增殖标志物，（c）AT8核tau表位，以及（d）全基因组DNA甲基化变化。我们的研究结果表明，紫檀芪根据细胞状态对细胞分裂周期产生不同的影响，在分化的类神经元细胞中观察到神经保护作用，但在诱导分裂的细胞中未观察到。此外，紫檀芪会改变DNA甲基化模式。这些结果表明，紫檀芪可能为分化的类神经元细胞提供神经保护优势。然而，需要进一步的研究通过检查食用含紫檀芪食物的人群中的特定生物标志物来在体内证实这些作用。
