title: Mitochondrial ferritin attenuates β-amyloid-induced neurotoxicity: reduction in oxidative damage through the Erk/P38 mitogen-activated protein kinase pathways.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  MtFt attenuated Aβ(25-35)-induced neurotoxicity and reduced oxidative damage through Erk/P38 kinase signaling.
  
  
  CONCLUSIONS
  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: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang, People's Republic of China.
authors: Wen-Shuang
authors: WS
authors: Wu
authors: Ya-Shuo
authors: YS
authors: Zhao
authors: Zhen-Hua
authors: ZH
authors: Shi
authors: Shi-Yang
authors: SY
authors: Chang
authors: Guang-Jun
authors: GJ
authors: Nie
authors: Xiang-Lin
authors: XL
authors: Duan
authors: Song-Min
authors: SM
authors: Zhao
authors: Qiong
authors: Q
authors: Wu
authors: Zhen-Ling
authors: ZL
authors: Yang
authors: Bao-Lu
authors: BL
authors: Zhao
authors: Yan-Zhong
authors: YZ
authors: Chang
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D034741:RNA, Small Interfering; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D045304:Cytochromes c; D005293:Ferritins; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3