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 Aβ(25-35) to establish an AD model. RESULTS: We report that knockdown of MtFt expression significantly enhanced Aβ(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 Aβ(25-35). Further, MtFt inhibited Aβ(25-35)-induced P38 mitogen-activated protein kinase and activated extracellular signal-regulated kinase (Erk) signaling. INNOVATION: MtFt attenuated Aβ(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.
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 Aβ(25-35) to establish an AD model. RESULTS: We report that knockdown of MtFt expression significantly enhanced Aβ(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 Aβ(25-35). Further, MtFt inhibited Aβ(25-35)-induced P38 mitogen-activated protein kinase and activated extracellular signal-regulated kinase (Erk) signaling. INNOVATION: MtFt attenuated Aβ(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.
Authors: Nora E Gray; Jeff Morré; Jeremiah Kelley; Claudia S Maier; Jan F Stevens; Joseph F Quinn; Amala Soumyanath Journal: J Alzheimers Dis Date: 2014 Impact factor: 4.472
Authors: Christine M Kusminski; Alexandra L Ghaben; Thomas S Morley; Ricardo J Samms; Andrew C Adams; Yu An; Joshua A Johnson; Nolwenn Joffin; Toshiharu Onodera; Clair Crewe; William L Holland; Ruth Gordillo; Philipp E Scherer Journal: Diabetes Date: 2019-12-27 Impact factor: 9.461