Zhang Issan, Maysinger Dusica, Beus Maja, Mravak Antonija, Yu Ziqi, Perić Bakulić Martina, Dion Patrick A, Rouleau Guy A, Bonačić-Koutecký Vlasta, Antoine Rodolphe, Sanader Maršić Željka
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, H3G 1Y6 Montreal, Canada.
Faculty of Science, University of Split, Ruđera Boškovića 33, 21000 Split, Croatia.
Nanoscale. 2025 Jan 2;17(2):1092-1104. doi: 10.1039/d4nr03512g.
This study focuses on the modulatory effects of gold nanoclusters with 25 gold atoms and 18 acetyl cysteines (AuAcCys) in human microglia, human iPSC-derived neurons and SH-SY5Y differentiated human neuronal cells. The combination of chemical, biological, and computational methods shows the well-retained viability of these human cells treated with AuAcCys, interactions between AuAcCys and transcription factor TFEB (computational approach), interactions between TFEB and HMGB1 (proximity ligation assay and molecular modeling using AlphaFold), modulation of the abundance and location of acHMGB1 by AuAcCys (immunocytochemistry), and the reduction of ROS in cells treated with AuAcCys (CellROX live imaging). These novel findings in human neural cells, particularly neurons, encourage further studies in experimental animal models of neurological disorders and/or human organoids to exploit the unique structural and photophysical properties of gold nanoclusters and to better understand their ability to modulate molecular mechanisms in human cells.
本研究聚焦于含有25个金原子和18个乙酰半胱氨酸的金纳米簇（AuAcCys）对人小胶质细胞、人诱导多能干细胞衍生神经元以及SH-SY5Y分化的人神经元细胞的调节作用。化学、生物学和计算方法相结合的研究表明，用AuAcCys处理后的这些人类细胞具有良好的活力，AuAcCys与转录因子TFEB之间存在相互作用（计算方法），TFEB与HMGB1之间存在相互作用（邻近连接分析和使用AlphaFold的分子建模），AuAcCys对乙酰化HMGB1的丰度和定位有调节作用（免疫细胞化学），以及用AuAcCys处理的细胞中活性氧的减少（CellROX实时成像）。这些在人类神经细胞尤其是神经元中的新发现，鼓励在神经疾病实验动物模型和/或人类类器官中开展进一步研究，以利用金纳米簇独特的结构和光物理性质，并更好地理解它们调节人类细胞分子机制的能力。
