Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats
Publication in refereed journal


摘要Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a role to reduce iron in the brain and hence has the potential to prevent or delay brain iron accumulation in iron-associated neurodegenerative disorders. Here, we investigated the effects of hepcidin expression adenovirus (ad-hepcidin) and hepcidin peptide on brain iron contents, iron transport across the brain-blood barrier, iron uptake and release, and also the expression of transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin 1 (Fpn1) in cultured microvascular endothelial cells and neurons. We demonstrated that hepcidin significantly reduced brain iron in iron-overloaded rats and suppressed transport of transferrin-bound iron (Tf-Fe) from the periphery into the brain. Also, the peptide significantly inhibited expression of TfR1, DMT1, and Fpn1 as well as reduced Tf-Fe and non-transferrin-bound iron uptake and iron release in cultured microvascular endothelial cells and neurons, while downregulation of hepcidin with hepcidin siRNA retrovirus generated opposite results. We concluded that, under iron-overload, hepcidin functions to reduce iron in the brain by downregulating iron transport proteins. Upregulation of brain hepcidin by ad-hepcidin emerges as a new pharmacological treatment and prevention for iron-associated neurodegenerative disorders.
著者Fang DU, Zhong-Ming QIAN, Qianqian LUO, Wing-Ho YUNG, Ka KE
期刊名稱Molecular Neurobiology
頁次101 - 114
關鍵詞Hepcidin,Brain iron homeostasis,Iron overload,Transferrin receptor-1 (TfR1),Divalent metal transporter 1 (DMT1),Ferroportin 1 (Fpn1),Transferrin-bound iron (Tf-Fe),Non-transferrin-bound iron (NTBI),Brain microvascular endothelial cell (BMEC)
Web of Science 學科類別Neurosciences;Neurosciences & Neurology

上次更新時間 2020-18-10 於 02:20