Investigation of therapeutic potential of cerium oxide nanoparticles in Alzheimer’s disease using transgenic Drosophila

Abstract

In the current study, the therapeutic potential of cerium oxide nanoparticles (nCeO₂) was investigated in a human tau (htau) model of Alzheimer’s disease (AD), using Drosophila melanogaster as an in vivo model. nCeO₂ synthesised via the hydroxide-mediated approach were characterised using Fourier transform infrared (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD) analyses and Raman spectroscopy. Characterisation studies confirmed the formation of pure cubic-structured nCeO₂ and showed that the particles were spherically shaped, with an average size between 20 and 25 nm. The synthesised nCeO₂ were then administered as part of the diet to transgenic Drosophila for one month, at 0.1 and 1 mM concentrations, and its effect on the biochemical levels of superoxide dismutase (SOD), acetylcholinesterase (AChE), and the climbing activity of flies were studied in a pan-neuronal model (elav; htau) of AD. Using an eye-specific model of htau expression (GMR; htau), the effect of nCeO₂ on htau and autophagy-related (ATG) gene expression was also studied. Dietary administration of nCeO₂ at a concentration of 1 mM restored the activity of SOD similar to that of control, but both concentrations of nCeO₂ failed to modulate the level of AChE, and did not elicit any significant improvements in the climbing activity of elav; htau flies. Moreover, nCeO₂ at a concentration of 1 mM significantly affected the climbing activity of elav; htau flies. nCeO₂ also elicited a significant decrease in htau gene expression at both concentrations and increased the mRNA expression of key autophagy genes ATG1 and ATG18. The results therefore indicate that nCeO₂ aids in replenishing the levels of SOD and tau clearance via the activation of autophagy.