期刊
ISCIENCE
卷 24, 期 5, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.102431
关键词
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资金
- National Natural Science Foundation of China [31871202, 31771124]
- Department of Science and Technology of Shandong Province [ZR2019MC057]
- Excellent Innovative Team of Shandong Province [2020KJK007]
- Taishan Scholars Construction Project, Shandong
The study found that apoferritin has a neuroprotective effect against MPTP-induced PD by inhibiting iron aggregation and modulating ferroptosis, providing a promising therapeutic target for the treatment of PD.
Iron deposition is one of the key factors in the etiology of Parkinson's disease (PD). Iron-free-apoferritin has the ability to store iron by combining with a ferric hydroxide-phosphate compound to form ferritin. In this study, we investigated the role of apoferritin in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice models and elucidated the possible underlying mechanisms. Results showed that apoferritin remarkably improved MPTP-induced motor deficits by rescuing dopaminergic neurodegeneration in the substantia nigra. Apoferritin inhibited MPTP-induced iron aggregation by down-regulating iron importer divalent metal transporter 1 (DMT1). Meanwhile, we also showed that apoferritin prevented MPTP-induced ferroptosis effectively by inhibiting the up-regulation of long-chain acyl-CoA synthetase 4 (ACSL4) and the down-regulation of ferroptosis suppressor protein 1 (FSP1). These results indicate that apoferritin exerts a neuroprotective effect against MPTP by inhibiting iron aggregation and modulating ferroptosis. This provides a promising therapeutic target for the treatment of PD.
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