title: Iron transport across the blood-brain barrier: development, neurovascular regulation and cerebral amyloid angiopathy.
abstract: 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.
authors.affiliation: Department of Biochemistry, University at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY, 14214, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: McCarthy
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kosman
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D007501:Iron / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron