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Molecular evidence of impaired iron metabolism and its association with Parkinson's disease progression

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Abstract

The aim of the study is to investigate the role of ATP-binding cassette subfamily B member 7 (ABCB7) in correlation with the progression of Parkinson’s disease. Initially, the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to develop a mouse model of mild and severe forms of Parkinson’s disease. Histology, immunohistology, and Western blotting were used to investigate the role of ABCB7 in disease progression. Mice injected with MPTP, at doses of 18 and 30 mg/kg for 10 and 15 consecutive days, respectively, developed mild and severe forms of Parkinson’s disease, respectively. Motor dysfunction is accessed through pole test in which, mild and severe forms of Parkinson’s disease developed mice takes 1.7 and 3.3 times more time to reach the floor than the control mice. Similarly, in rotarod test, the progression of Parkinson’s disease is evident with the progressive loss of motor stability. Histologically, the progression of Parkinson’s disease is evident with formation of cell aggregates in mild form; with the formation of more Lewy body structure and tissue hardening in a severe form of Parkinson’s disease. Immunohistochemistry showed gradual upregulation of ABCB7 in the cellular cytoplasm in mild stage Parkinson’s disease, while significant overexpression of ABCB7 was observed in the severe forms. Western blotting results confirmed 1.6- and 2.9-fold overexpression of ABCB7 in mild and severe forms of Parkinson’s disease, respectively. Collectively, the results showed that ABCB7 was present during Parkinson’s disease progression. However, upregulation of ABCB7 increased the cytoplasm level of the iron–sulfur complex, which negatively regulated the iron-dependent protein and can be used to determine the progression of Parkinson’s disease.

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Authors and Affiliations

  1. Department of Neurology, Dalian University Affiliated Xinhua Hospital, No. 156 Wansui Street, Dalian, 116021, Liaoning, China

    Haitao Chi, Wei Tang & Ying Bai

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  1. Haitao Chi
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  2. Wei Tang
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  3. Ying Bai
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Contributions

HC, YB: study design; WT: collected the samples; HC, YB: laboratory work; All authors: contributed to the manuscript, read, and approved the final manuscript.

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Correspondence to Ying Bai.

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The authors of this work declare that they have no conflict of interest.

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Animal used in the experiments and protocols followed were approved by Institutional ethical and animal care committee.

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Chi, H., Tang, W. & Bai, Y. Molecular evidence of impaired iron metabolism and its association with Parkinson's disease progression. 3 Biotech 10, 173 (2020). https://doi.org/10.1007/s13205-020-2162-1

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