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Insights into the Impact of Gold Nanoclusters Au10SG10 on Human Microglia

The purpose of the current study is to uncover the impact of small liganded gold nanoclusters with 10 gold atoms and 10 glutathione ligands (Au10SG10) on several biomarkers in human microglia. We established the links connecting the atomically precise structure of Au10SG10 with their properties and changes in several biomolecules under oxidative stress. Au10SG10 caused the loss of mitochondrial metabolic activity, increased lipid peroxidation and translocation of an alarmin molecule, high mobility group box 1 (HMGB1), from the nucleus to the cytosol. Molecular modeling provided an insight into the location of amino acid interaction sites with Au10SG10 and the nature of bonds participating in these interactions. We show that Au10SG10 can bind directly to the defined sites of reduced, oxidized, and acetylated HMGB1. Further studies with similar complementary approaches merging live-cell analyses, determination of biomarkers, and cell functions could lead to optimized gold nanoclusters best suited for diagnostic and bioimaging purposes in neuroscience.

gold nanocluster ; microglia ; HMGB1 ; cell death ; lipid peroxidation ; glutathione ; oxidative stress ; molecular modeling ; QM/MM simulations

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