Mitochondrial Ferritin Attenuates β-Amyloid-Induced Neurotoxicity: Reduction in Oxidative Damage Through the Erk/P38 Mitogen-Activated Protein Kinase Pathways

Aims: Mitochondrial ferritin (MtFt), which was recently discovered, plays an important role in preventing neuronal damage in 6-hydroxydopamine-induced Parkinsonism by maintaining mitochondrial iron homeostasis. Disruption of iron regulation also plays a key role in the etiology of Alzheimer's disease (AD). To explore the potential neuroprotective roles of MtFt, rats and cells were treated with A beta(25-35) to establish an AD model. Results: We report that knockdown of MtFt expression significantly enhanced A beta(25-35)-induced neurotoxicity as shown by dysregulation of iron homeostasis, enhanced oxidative stress, and increased cell apoptosis. Opposite results were obtained when MtFt was overexpressed in SH-SY5Y cells prior to treatment with A beta(25-35). Further, MtFt inhibited A beta(25-35)-induced P38 mitogen-activated protein kinase and activated extracellular signal-regulated kinase (Erk) signaling. Innovation: MtFt attenuated A beta(25-35)-induced neurotoxicity and reduced oxidative damage through Erk/P38 kinase signaling. Conclusion: Our results show a protective role of MtFt in AD and suggest that regulation of MtFt expression in neuronal cells may provide a new neuroprotective strategy for AD. Antioxid. Redox Signal. 18, 158-169.