Ferroportin1 in the brain

Despite years of research, it remains unclear why certain brain regions of patients with neurodegenerative diseases (NDs) have abnormally high levels of iron, although it has long been suggested that disrupted expression of iron-metabolizing proteins due to genetic or non-genetic factors is responsible for the enhancement in brain iron contents. In addition to the increased expression of cell-iron importers lactoferrin (lactotransferrin) receptor (LfR) in Parkinsonʼs disease (PD) and melanotransferrin (p97) in Alzheimerʼs disease (AD), some investigations have suggested that cell-iron exporter ferroportin 1 (Fpn1) may be also associated with the elevated iron observed in the brain. The decreased expression of Fpn1 and the resulting decrease in the amount of iron excreted from brain cells has been thought to be able to enhance iron levels in the brain in AD, PD and other NDs. Cumulative results also suggest that the reduction of Fpn1 can be induced by hepcidin-dependent and -independent pathways. In this article, we discuss the current understanding of Fpn1 expression in the brain and cell lines of rats, mice and humans, with emphasis on the potential involvement of reduced Fpn1 in brain iron enhancement in patients with AD, PD and other NDs. •Abnormally iron accumulation in certain brain regions have been demonstrated in some neurodegenerative diseases.•The reduced expression of Fpn1 may be one of the reasons for iron accumulation in the brain of some neurodegenerative diseases.•The reduced expression of ferroportin 1 can be caused by hepcidin-dependent and -independent pathways.