Mitochondrial ferritin attenuates β-amyloid-induced neurotoxicity: Reduction in oxidative damage through the Erk/P38 mitogen-activated protein kinase pathways

Wen Shuang Wu, Ya Shuo Zhao, Zhen Hua Shi, Shi Yang Chang, Guang Jun Nie, Xiang Lin Duan, Song Min Zhao, Qiong Wu, Zhen Ling Yang, Bao Lu Zhao, Yan Zhong Chang

Research output: Contribution to journalArticle

54 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)158-169
Number of pages12
JournalAntioxidants and Redox Signaling
Volume18
Issue number2
DOIs
StatePublished - Jan 10 2013

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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