Title : Effects of copper nanoparticle-induced reactive oxygen species and carbon nanodots on amyloid beta protein aggregation: Relevance in neurodegenerative diseases
Free radical-mediated beta amyloid protein radicalization, lipid peroxidation and DNA damage are all implicated in neuronal cell damage causing many debilitating neurodegenerative diseases. Alzheimer’s disease is the most common form of dementia among those with neurodegenerative illness that have affected more than 24 million people globally. Material including metals at nanoscale with reducing power have been known to cause free radical generation, which consequently can induce radicalization, mis-folding, and aggregation of beta amyloid (βA) proteins. In this study, we measured the level of protein-DMPO nitrone adducts, a quantitative indicator of free radical production, by using anti-DMPO adduct antibodies at different concentrations of copper nanoparticles (CuNP) as a source of reactive oxygen species (ROS). Lyophilized form of βA proteins as well as βA proteins from IMR-32 cells (In Vitro conditions) were tested for their aggregation levels in the presence of CuNP. As a way to identify the protein aggregation sites, Confocal light microscope technique was also introduced. We also evaluated the potential efficacy of applying carbon nanodots (CNDs) that has ROS scavenging character as a detoxifying agent. The results indicated that, 1) CuNP carries a potential to be a source for ROS generation that can enhance the aggregation mechanism of βA proteins, 2) βA protein aggregation level is proportional to the concentration of CuNP present in the reaction, 3) βA proteins, both from lyophilized and In Vitro sources, were equally effected by the ROS from CuNP, 4) βA protein aggregates were observed in both cytoplasm and nucleus in Confocal images, and 5) CNDs can prevent βA protein aggregation before and after cell exposure to CuNP. From our study, it is concluded that ROS generation can be a contributing process for βA protein aggregation through a radicalizing process and the effects of ROS on protein aggregation can be reduced or even reversed by the presence of CNDs, a ROS scavenger.
Audience Take Away:
Audience will learn about exposure related potential toxicity issues of nanomaterial in neurodegenerative diseases including Alzheimer’s disease.
For those working in the field of environmental/public health, they may be able to use the experimental data as a reference point for conducting similar studies.
The results from this study should be able to provide some insights about the roles of ROS from exogenous sources including engineered nano-metal.
The information about the exposure doses related to CuNP should help design similar types of studies.
The information about LD50 and max threshold levels of reagents used in this study should be benefit others working in neurodegenerative diseases.