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Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson's disease
Ci,Yun Zhe1,2; Li,Haiyan1; You,Lin Hao1; Jin,Yu1; Zhou,Rui1; Gao,Guofen1; Hoi,Maggie Pui Man3; Wang,Chunyan2; Chang,Yan Zhong1; Yu,Peng1
Source PublicationNeurochemistry International

Parkinson's disease (PD) is accompanied by iron overload in the brain. However, whether iron accumulation is the cause or effect of PD is still unknown. Iron regulatory protein 2 (IRP2) plays a critical role in keeping iron homeostasis, and our previous data showed that the deletion of the IRP2 gene caused iron deposits in organs of mice. Therefore, we further investigated the role of iron overload induced by IRP2 gene deletion in the development of the MPTP-induced PD mouse model in vivo, and the underlying regulatory mechanisms in primary cultures of astrocytes in vitro. Data from neurobehavioral, immunohistochemistry, TUNEL and Elisa studies showed that MPTP treatment enhanced the symptoms of PD in vivo, increased cell apoptosis and decreased dopamine levels in IRP2 mice. In addition, the expression of L-ferritin and iron contents increased significantly in the substantia nigra (SN) of IRP2 mice. Moreover, MPTP treatment significantly increased the expression of DMT1 (-IRE) and decreased the expression of TfR1 in IRP2 mice. Further investigations with primary cultures of astrocytes from IRP2 mice showed that MPP increased the expression of L-ferritin and DMT1 (-IRE), and decreased the expression of TfR1. Our results demonstrated that IRP2 gene deletion induced iron accumulation in the SN, which exacerbated the neuronal apoptosis and Parkinsonism symptoms. At the same time, IRP2 gene deletion increased the iron contents in astrocytes around neurons, which further decreased their protection for neurons and increased the cell apoptosis, ultimately forming a vicious cycle that leads to the onset and progression of PD.

KeywordAstrocyte Dmt1 Iron Iron Regulatory Protein 2 Parkinson's Disease
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Indexed BySCIE
WOS Research AreaBiochemistry & Molecular Biology ; Neurosciences & Neurology
WOS SubjectBiochemistry & Molecular Biology ; Neurosciences
WOS IDWOS:000518704200012
Scopus ID2-s2.0-85077661515
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorChang,Yan Zhong; Yu,Peng
Affiliation1.Laboratory of Molecular Iron Metabolism,Key Laboratory of Animal Physiology,Biochemistry and Molecular Biology,College of Life Sciences,Shijiazhuang,050024,China
2.Department of Histology and Embryology,Basic Medical College,Chengde Medical University,Chengde,067000,China
3.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao,Macao
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GB/T 7714
Ci,Yun Zhe,Li,Haiyan,You,Lin Hao,et al. Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson's disease[J]. Neurochemistry International,2020,134.
APA Ci,Yun Zhe,Li,Haiyan,You,Lin Hao,Jin,Yu,Zhou,Rui,Gao,Guofen,Hoi,Maggie Pui Man,Wang,Chunyan,Chang,Yan Zhong,&Yu,Peng.(2020).Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson's disease.Neurochemistry International,134.
MLA Ci,Yun Zhe,et al."Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson's disease".Neurochemistry International 134(2020).
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