Iron dysregulation and ferroptosis have emerged as critical factors to the onset and progression of Alzheimer's Disease (AD), where cell death ultimately deteriorates cognitive functions such as memory and learning. Therapeutic interventions preventing or delaying cell death while promoting cellular repair in the central nervous system (CNS) could mitigate AD progression. In the brain, repair is primarily regulated by neural stems cells (NSCs), astrocytes, and microglia, with antioxidants supporting tissue repair by reducing oxidative stress and preserving mitochondrial function. Therefore, understanding how iron dysregulation impairs regenerative mechanisms – and whether antioxidant treatment can restore them - is of critical focus to the biomedical community.
This study investigates how Idebenone, a synthetic antioxidant, can attenuate FIN56-induced ferroptosis in CNS cells to promote cellular survival and repair. Using a CNS cell ferroptosis model previously established by our lab, we induce iron dysregulation with FIN56 and treat cells with varying concentrations of Idebenone. We hypothesize that Idebenone will reduce oxidative stress caused by FIN56, therefore restoring mitochondrial function and cell viability.
We assess oxidative stress, lipid peroxidation, Reactive Oxygen Species (ROS) production, and mitochondrial health using immunofluorescence assays, JC-1, and MitoSOX. DNA is quantified using the Picogreen assay to evaluate cell survival, while confocal microscopy visualizes changes in cell morphology and shape. Preliminary findings suggest Idebenone is capable of reversing ROS accumulation and lipid peroxidation in human astrocytes (HAa). Early results also indicate cell-dependent responses, with potential restoration of mitochondrial function and cell viability.