en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="line-height:2;"><strong>Introduction</strong>: 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.<br> <strong>Methods</strong>: 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&rsquo;s disease such as amyloid precursor protein (APP) expression, A&beta; aggregation, soluble APP&alpha;, and APP&beta; secretion were also investigated in hippocampal cells treated with various concentrations of nanoparticle (NP) for different exposure times.<br> <strong>Results</strong>: Our results revealed that Fe2O3-NP treatment causes oxidative stress in cells which is accompanied by upregulation of the APP and A&beta; in a concentration-dependent manner. NP exposure also leads to more secretion of sAPP&beta; rather than sAPP&alpha;, leading to increased activation of &beta;-secretase in NP-received cells. All the harmful effects accumulate in neurons that cannot be renovated, leading to neurodegeneration in Alzheimer&rsquo;s disease.<br> <strong>Conclusion</strong>: This study approved iron-based NPs could help to develop Alzheimer&rsquo;s and related neurological disorders and explained why some of the iron chelators have therapeutic potential in Alzheimer&rsquo;s disease.</span></span></span></div> Aβ deposition, Neurodegeneration, Oxidative stress, Hippocampal cells, Amyloid precursor protein (APP) 203 212 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2005-1&slc_lang=en&sid=1 Leila Sadeghi l.sadeghi@tabrizu.ac.ir 13700319475328460044852 13700319475328460044852 Yes Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. Arezu Marefat arezum86@gmail.com 13700319475328460044853 13700319475328460044853 No Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.