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         headline:Benefits of Iron Chelators in the Treatment of Parkinson’s Disease
         description:As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson’s disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.
         datePublished:2021-03-01T00:00:00Z
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            Iron deposition
            Ferroptosis
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      headline:Benefits of Iron Chelators in the Treatment of Parkinson’s Disease
      description:As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson’s disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.
      datePublished:2021-03-01T00:00:00Z
      dateModified:2021-03-01T00:00:00Z
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         Parkinson’s disease
         Iron deposition
         Ferroptosis
         Iron chelator
         Neuroprotective effect
         Neurosciences
         Neurochemistry
         Biochemistry
         general
         Cell Biology
         Neurology
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      name:Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, China
      name:Department of Infectious Diseases, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
      name:Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, China

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