Title : Effects of Particulate Matter-Induced Reactive Oxygen Species and Carbon nanodots on Amyloid Beta Protein Aggregation: Relevance in Neurodegenerative Diseases
Abstract:
Alzheimer’s Disease is one of the most common neurodegenerative illness with multiple etiological mechanisms explored. Accumulation of different sizes of beta amyloid (βA) proteins generated from Amyloid Protein Precursors (APPs) is known to induce a plaque formation. In a typical beta-amyloidogenic APP metabolism, about 90 percent of βA proteins are those with 40-amino acids while 42-amino acids make up the rest. Initiation of the plaque formation or aggregation process of related proteins can be induced by various mechanisms. Regardless, the presence of Reactive Oxygen Species (ROS) and free radicals is known to be one of the pathological mechanisms like other common forms of diseases. As a source for ROS and free radicals, we have tested a potential role of the particulate matter (PM) collected from residential indoor settings in the aggregation of the lyophilized βA proteins. PM is well known as an inducer of inflammatory process in many biological organisms, and ROS and free radicals from the PM are believed to be the causal agents. In our study, lyophilized forms of βA proteins were used to test their aggregation properties in the presence of indoor PM extracts at different concentrations. The same PM extracts were used as a source of ROS in the presence of anti-DMPO adduct antibodies for assessing the aggregation level of βA protein generated by IMR-32 cells. Radicalized βA proteins were bound by DMPO nitron adduct which was identified by anti-DMPO antibody. Then secondary antibody was used for quantifying purpose through ELISA. The aggregation extent was also visualized by using Con-focal imaging. Results indicated that: 1) PM extracts showed a potential to induce aggregation of lyophilized βA proteins, 2) βA proteins aggregation is proportional to the level of PM exposed, 3) Aggregation extent of the βA proteins in In Vitro settings was consistent with the case of lyophilized proteins, 4) The formation of aggregates was confirmed by Con-focal imaging, and 5) Carbon nanodots have protective effects through ROS scavenging potential. From the results, it is concluded that poor air quality induced by PM exposure, especially chronic exposure conditions, is a potential etiological mechanism of Alzheimer’s disease by inducing plaque formation in the brain tissues. The level and the duration of exposure to PM before clinical symptoms start showing would be an area for investigation in the coming years.
