Song Li-Mei, Xiao Zhi-Xin, Zhang Na, Yu Xiao-Qi, Cui Wei, Xie Jun-Xia, Xu Hua-Min
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.
iScience. 2021 Apr 16;24(5):102431. doi: 10.1016/j.isci.2021.102431. eCollection 2021 May 21.
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.
铁沉积是帕金森病（PD）病因中的关键因素之一。无铁脱铁铁蛋白具有通过与氢氧化铁 - 磷酸盐化合物结合形成铁蛋白来储存铁的能力。在本研究中，我们研究了脱铁铁蛋白在1 - 甲基 - 4 - 苯基 - 1,2,3,6 - 四氢吡啶（MPTP）诱导的PD小鼠模型中的作用，并阐明了可能的潜在机制。结果表明，脱铁铁蛋白通过挽救黑质中的多巴胺能神经变性，显著改善了MPTP诱导的运动缺陷。脱铁铁蛋白通过下调铁转运蛋白二价金属转运体1（DMT1）来抑制MPTP诱导的铁聚集。同时，我们还表明脱铁铁蛋白通过抑制长链酰基辅酶A合成酶4（ACSL4）的上调和铁死亡抑制蛋白1（FSP1）的下调，有效预防了MPTP诱导的铁死亡。这些结果表明，脱铁铁蛋白通过抑制铁聚集和调节铁死亡对MPTP发挥神经保护作用。这为PD的治疗提供了一个有前景的治疗靶点。
