Deferoxamine attenuates iron-induced oxidative stress and prevents mitochondrial aggregation and α-synuclein translocation in SK-N-SH cells in culture

One of the defining characteristics of neurodegenerative diseases, including Parkinson's disease, is an abnormal accumulation of iron in the affected brain areas. By using SK-N-SH, a dopaminergic cell line, we have found that iron (100-250 μM FeSO₄) decreased cell viability, increased lipid peroxidation, and the said effects were blocked by deferoxamine (DFO: 10 μM). Furthermore, DFO, in the absence of iron, enhanced the level of adenosine triphosphate (ATP), but caused chromatin condensation and cell death. Morphological studies revealed that iron (50-100 μM) altered mitochondrial morphology, disrupted nuclear membrane, and translocated α-synuclein from perinuclear region into the disrupted nucleus. The results of these studies suggest that DFO is able to block and attenuate iron-mediated oxidative stress. However, in the absence of excess iron, DFO itself may have deleterious effects on the morphology and hence integrity of dopaminergic neurons.