Benefits of Iron Chelators in the Treatment of Parkinson's Disease.
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.
['Zeng|Xiaoyan|X|', 'An|Hedi|H|', 'Yu|Fei|F|', 'Wang|Kai|K|', 'Zheng|Lanlan|L|', 'Zhou|Wei|W|', 'Bao|Yiwen|Y|', 'Yang|Jie|J|', 'Shen|Nan|N|', 'Huang|Dongya|D|']
D000818:Animals D017209:Apoptosis D045744:Cell Line, Tumor D002470:Cell Survival D003676:Deferoxamine D059290:Dopaminergic Neurons D005290:Ferric Compounds D000079403:Ferroptosis D006801:Humans D007502:Iron Chelating Agents D019190:Iron Overload D020932:Nerve Growth Factor D018696:Neuroprotective Agents D010302:Parkinson Disease, Secondary D000644:Quaternary Ammonium Compounds D011810:Quinoxalines D051381:Rats D017382:Reactive Oxygen Species D013141:Spiro Compounds
Iron chelator Ferroptosis Iron deposition Neuroprotective effect Parkinson’s disease