Gold nanoclusters Au₂₅AcCys₁₈ normalize intracellular ROS without increasing cytoplasmic alarmin acHMGB1 abundance in...

This study focuses on the modulatory effects of gold nanoclusters with 25 gold atoms and 18 acetyl cysteines (Au₂₅AcCys₁₈) 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 Au₂₅AcCys₁₈, interactions between Au₂₅AcCys₁₈ 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 Au₂₅AcCys₁₈ (immunocytochemistry), and the reduction of ROS in cells treated with Au₂₅AcCys₁₈ (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.