Nanozymes: modulators of neural cells

点击翻译按钮获取中文摘要

The exciting studies we completed in the last five years on the use and behavior of nanostructures with neural cells have led us to propose studies on nanozymes. Why nanozymes? Nanozymes are nanostructures that mimic enzymatic activities. They are considered the next generation of artificial enzymes and have been of high interest for multidisciplinary investigations due to their stability, unique surface properties and low cost of production. Still, many properties can be improved for their wide application as nanotools and nanosensors. Our hypothesis is that gold nanocluster (AuNC) nanozymes of selected shapes, sizes and surface ligands will fine-tune redox-regulating enzymes in human cells, thereby maintaining homeostasis disrupted by lipotoxins. Our long-term objective is to uncover which surface ligands on AuNC promote or abolish beneficial redox changes in glial cells exposed to lipotoxins from high-fat food containing high levels of saturated acids (e.g. palmitic acid and peroxidized unsaturated acids). We are particularly interested in several key signal transduction pathways to reveal the steps at which nanozymes (alone or combined with selected modulators of signaling molecules) can be assessed. The experimental approaches are applicable to many cell types and other enzymatic systems beyond redox regulators. We aim to improve physiological cell functions by combining nanozymes with small amounts of natural enzymes or small nucleolar RNA (snoRNA). Our short-term objectives are: 1. to establish which ligands can best improve redox enzymatic activity (catalase, peroxidase, dismutase, thioredoxin reductase); 2. to generate integrated nanozymes (INAzymes) combining nanozymes with natural enzymes, thereby enhancing beneficial enzymatic activity and 3. to show that nanozymes and INAzymes are effective in human cell models, including neural cells exposed to various insults. Gold nanoclusters have a precise number of atoms arranged in specific spatial locations. We propose to study AuNC with 10 to 25 gold atoms because they are well characterized. Their surfaces can be modified to improve their enzymatic activities and minimize or eliminate toxicity. Significance. Our results will show why and how gold nanoclusters can alter redox status in human cells under different stressful conditions, including those caused by food rich in saturated fatty acids and their metabolic products. The production and handling of AuNC are environmentally-friendly and cost effective. The proposed studies are an excellent training platform for students at different levels interested in the effects of nanostructures at the cellular level, not only in metaflammation but also following diverse insults and associated redox impairments.