caa a22 4500 60617656X CHVBK 20210128100748.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00018-014-1771-4 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1771-4 Iron transport across the blood-brain barrier: development, neurovascular regulation and cerebral amyloid angiopathy [Elektronische Daten] [Ryan McCarthy, Daniel Kosman] There are two barriers for iron entry into the brain: (1) the brain-cerebrospinal fluid (CSF) barrier and (2) the blood-brain barrier (BBB). Here, we review the literature on developmental iron accumulation by the brain, focusing on the transport of iron through the brain microvascular endothelial cells (BMVEC) of the BBB. We review the iron trafficking proteins which may be involved in the iron flux across BMVEC and discuss the plausible mechanisms of BMVEC iron uptake and efflux. We suggest a model for how BMVEC iron uptake and efflux are regulated and a mechanism by which the majority of iron is trafficked across the developing BBB under the direct guidance of neighboring astrocytes. Thus, we place brain iron uptake in the context of the neurovascular unit of the adult brain. Last, we propose that BMVEC iron is involved in the aggregation of amyloid-β peptides leading to the progression of cerebral amyloid angiopathy which often occurs prior to dementia and the onset of Alzheimer's disease. Springer Basel, 2014 Iron nationallicence Blood-brain barrier nationallicence Astrocytes nationallicence Transferrin nationallicence Amyloid precursor protein nationallicence 6-OHDA : 6-Hydroxydopamine nationallicence APP : Amyloid-β precursor protein nationallicence sAPP : Soluble β-secretase-cleaved APP nationallicence Aβ : Amyloid-β nationallicence BBB : Blood-brain barrier nationallicence BMVEC : Brain microvascular endothelial cells nationallicence CNS : Central nervous system nationallicence Cp : Ceruloplasmin nationallicence CSF : Cerebrospinal fluid nationallicence CTFβ : β-Carboxyl-terminal fragment nationallicence Dcytb : Duodenal cytochrome b nationallicence DMT1 : Divalent metal transporter 1 nationallicence E ° : Electrochemical potential nationallicence Fpn : Ferroportin nationallicence GPI : Glycosylphosphatidylinositol-anchor nationallicence hBMVEC : Human brain microvascular endothelial cell line nationallicence H-Ferritin : Heavy chain ferritin nationallicence Hp : Hephaestin nationallicence IRE : Iron-responsive element nationallicence IRP : Iron regulatory protein nationallicence L-Ferritin : Light chain ferritin nationallicence P# : Postnatal day # nationallicence sCp : Soluble ceruloplasmin nationallicence SDR2 : Stromal cell-derived receptor 2 nationallicence Steap : Six transmembrane epithelial antigen of the prostate nationallicence Tf : Transferrin nationallicence TfR : Transferrin receptor nationallicence Zip8 : Zrt/Irt-like protein 8 nationallicence Zip14 : Zrt/Irt-like protein 14 nationallicence Zp : Zyklopen nationallicence McCarthy Ryan Department of Biochemistry, University at Buffalo, School of Medicine and Biomedical Sciences, 14214, Buffalo, NY, USA aut Kosman Daniel Department of Biochemistry, University at Buffalo, School of Medicine and Biomedical Sciences, 14214, Buffalo, NY, USA aut Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 709-727 1420-682X 72:4<709 2015 72 18 https://doi.org/10.1007/s00018-014-1771-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1771-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- McCarthy Ryan Department of Biochemistry, University at Buffalo, School of Medicine and Biomedical Sciences, 14214, Buffalo, NY, USA aut NATIONALLICENCE 700 1- Kosman Daniel Department of Biochemistry, University at Buffalo, School of Medicine and Biomedical Sciences, 14214, Buffalo, NY, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 709-727 1420-682X 72:4<709 2015 72 18