Apoferritin improves motor deficits in MPTP-treated mice by regulating brain iron metabolism and ferroptosis
Li-Mei Song,
Zhi-Xin Xiao,
Na Zhang,
Xiao-Qi Yu,
Wei Cui,
Jun-Xia Xie,
Hua-Min Xu
Affiliations
Li-Mei Song
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, 266071, China
Zhi-Xin Xiao
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, 266071, China
Na Zhang
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, 266071, China; Institute of Brain Science and Disease, Qingdao University, Qingdao, China
Xiao-Qi Yu
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, 266071, China; Institute of Brain Science and Disease, Qingdao University, Qingdao, China
Wei Cui
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, 266071, China
Jun-Xia Xie
Institute of Brain Science and Disease, Qingdao University, Qingdao, China; Corresponding author
Hua-Min Xu
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, School of Basic Medicine, Qingdao University, Qingdao, 266071, China; Institute of Brain Science and Disease, Qingdao University, Qingdao, China; Corresponding author
Summary: 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.
