Zhang Na, Yu Xiaoqi, Xie Junxia, Xu Huamin
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, 266071, China.
Mol Neurobiol. 2021 Jun;58(6):2812-2823. doi: 10.1007/s12035-020-02277-7. Epub 2021 Jan 28.
Growing evidence has indicated that iron deposition is one of the key factors leading to neuronal death in the neurodegenerative diseases. Ferritin is a hollow iron storage protein composed of 24 subunits of two types, ferritin heavy chain (FTH) and ferritin light chain (FTL), which plays an important role in maintaining iron homeostasis. Recently, the discovery of extracellular ferritin and ferritin in exosomes indicates that ferritin might be not only an iron storage protein within the cell, but might also be an important factor in the regulation of tissue and body iron homeostasis. In this review, we first described the structural characteristics, regulation and the physiological functions of ferritin. Secondly, we reviewed the current evidence concerning the mechanisms underlying the secretion of ferritin and the possible role of secreted ferritin in the brain. Then, we summarized the relationship between ferritin and the neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD) and neuroferritinopathy (NF). Given the importance and relationship between iron and neurodegenerative diseases, understanding the role of ferritin in the brain can be expected to contribute to our knowledge of iron dysfunction and neurodegenerative diseases.
越来越多的证据表明,铁沉积是导致神经退行性疾病中神经元死亡的关键因素之一。铁蛋白是一种由铁蛋白重链(FTH)和铁蛋白轻链(FTL)两种类型的24个亚基组成的中空铁储存蛋白,在维持铁稳态中起重要作用。最近,细胞外铁蛋白和外泌体中铁蛋白的发现表明,铁蛋白可能不仅是细胞内的一种铁储存蛋白,而且可能是调节组织和机体铁稳态的一个重要因素。在这篇综述中,我们首先描述了铁蛋白的结构特征、调节及其生理功能。其次,我们综述了目前有关铁蛋白分泌机制及分泌型铁蛋白在大脑中可能作用的证据。然后,我们总结了铁蛋白与神经退行性疾病(包括帕金森病(PD)、阿尔茨海默病(AD)和神经铁蛋白病(NF))之间的关系。鉴于铁与神经退行性疾病的重要性及二者之间的关系,了解铁蛋白在大脑中的作用有望增进我们对铁功能障碍和神经退行性疾病的认识。