The Effect of Different Types of Nanoparticles on FUS and TDP-43 Solubility and Subcellular Localization

Increased environmental pollution has been suggested as one of the possible causes for increased incidence of neurodegenerative and developmental disorders. Through the environmental pollution, everyday consumer products and nanomedical applications, we are also exposed to various nanoparticles (NPs). Specific types of NPs have been shown to be able to cause neural damage in vivo through processes such as disruption of the blood-brain barrier, induction of neuroinflammation, increase in oxidative stress and protein aggregation. In this study, we analysed the influence of PEI-coated magnetic NPs designed for biotechnological applications and industrial SiO₂, TiO₂ N and TiO₂ P25 NPs on intracellular localization and solubility of fused in farcoma (FUS) and TAR-DNA binding protein 43 (TDP-43) that are important pathological hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). SH-SY5Y neuroblastoma cells and B16 mouse melanoma cells were exposed to NPs for 24 h and analysed using confocal microscopy and Western blot. Exposure to 50 μg/ml TiO₂ N and 4 μg/ml PEI NPs in SH-SY5Y cells caused cell toxicity-induced changes in expression in different biochemical/cellular fractions for both FUS and TDP-43 proteins. TiO₂ N induced a drop in nuclear levels of TDP-43 and increase in cytoplasmic levels of FUS, while PEI NPs increased nuclear levels of FUS. Furthermore, TiO₂ N and PEI induced a reduction of FUS and TDP-43 quantity in the less soluble urea fraction. No formation of stress granules was observed. These results demonstrate that TiO₂ N and PEI NPs can affect the behaviour of FUS and TDP-43 proteins; however, the changes were relatively minor compared to pathological changes even for the high NP concentrations (50 μg/ml) used in this study.