Investigation of the Iron Oxide Nanoparticle Effects on Amyloid Precursor Protein Processing in Hippocampal Cells

Iron oxide nanoparticles (Fe2O3-NPs) are small magnetic particles that are widely used in different aspects of biology and medicine in modern life. Fe2O3-NP accumulated in the living cells due to the absence of an active system to excrete the iron ions and damages cellular organelles by high reactivity.

Herein cytotoxic effects of Fe2O3-NP with a size of 50 nm on the primary culture of neonatal rat hippocampus were investigated using 2,5-diphenyltetrazolium bromide (MTT) assay. Pathophysiological signs of Alzheimer’s disease such as amyloid precursor protein (APP) expression, Aβ aggregation, soluble APPα, and APPβ secretion were also investigated in hippocampal cells treated with various concentrations of nanoparticle (NP) for different exposure times.

Our results revealed that Fe2O3-NP treatment causes oxidative stress in cells which is accompanied by upregulation of the APP and Aβ in a concentration-dependent manner. NP exposure also leads to more secretion of sAPPβ rather than sAPPα, leading to increased activation of β-secretase in NP-received cells. All the harmful effects accumulate in neurons that cannot be renovated, leading to neurodegeneration in Alzheimer’s disease.

This study approved iron-based NPs could help to develop Alzheimer’s and related neurological disorders and explained why some of the iron chelators have therapeutic potential in Alzheimer’s disease.