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

Abstract 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 Aβ25–35 to establish an AD model. Results: We report that knockdown of MtFt expression significantly enhanced Aβ25–35-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 Aβ25–35. Further, MtFt inhibited Aβ25–35-induced P38 mitogen-activated protein kinase and activated extracellular signal-regulated kinase (Erk) signaling. Innovation: MtFt attenuated Aβ25–35-induced neurotoxicity and reduced oxidative damage through Erk/P38 kinase signa...