Gold nanoclusters Au ₂₅ AcCys ₁₈ normalize intracellular ROS without increasing cytoplasmic alarmin acHMGB1 abundance in human microglia and neurons

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.