Keele Research Repository

Ferroptosis is a non-apoptotic, iron-dependent cell death pathway first identified in an engineered tumorigenic cell line in 2012. Hallmark characteristics include direct or indirect loss of functional GPX4 enzymes, resulting in depletion of glutathione and upregulated lipid peroxidation. The alignment of these (and other) characteristics with those reportedly resulting from dopaminergic degeneration in Parkinson’s disease provides an interesting avenue for research – does ferroptosis play a role in Parkinson’s disease pathology? SH-SY5Y cells, utilised as an in vitro model of Parkinson’s disease, were treated with erastin (the first identified ferroptosis inducer), either alone or in combination with DHA (an ω-3 polyunsaturated fatty acid), AACOCF3 (an inhibitor of cPLA2), BEL (an inhibitor of iPLA2β) or Fer-1 (an ROS-scavenging inhibitor of ferroptosis). MTT cell viability assay determined these cells to be undergoing significant cell death induced by erastin, though the lack of significant difference when cells were co-treated with the additional compounds suggests the cell death pathway induced may not be ferroptosis. Repeating the experiment using trypan blue to measure cell viability failed to uncover any significant cell death over the same concentration range of erastin. TEM investigation was also conducted with these erastin concentrations, and determined a lack of cell death, in addition to a lack of shrunken mitochondria (considered the gold standard morphological observation in ferroptotic identification). Possible explanations for these discrepancies and potential further work are also discussed.