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Title:
Iron transport across the blood–brain barrier: development, neurovascular regulation and cerebral amyloid angiopathy | Cellular and Molecular Life Sciences
Description:
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.
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Keywords {🔍}

pubmed, google, scholar, cas, iron, central, brain, transferrin, biol, cell, ferroportin, cells, rat, protein, chem, physiol, expression, res, transport, transporter, uptake, ceruloplasmin, human, sci, mol, cellular, amyloid, biochem, barrier, receptor, neurosci, bloodbrain, endothelial, astrocytes, blood, hepcidin, precursor, ferritin, article, proteins, mechanism, alzheimers, disease, metal, zip, copper, proc, divalent, hephaestin, distribution,

Topics {✒️}

month download article/chapter blood–brain–cerebrospinal fluid system β-amyloid precursor protein cyclic amp-protein kinase autosomal-dominant hemochrom-atosis colorimetric ferrozine-based assay amyloid-β peptides leading central nervous system metal cation-binding sites cerebral β-amyloid deposition 31p-mrs-based determination plasma membrane proton-adenosinetriphosphatases n-lobe monoferric transferrins iron-regulating protein hepcidin cells expressing gpi-ceruloplasmin anti-transferrin receptor antibody disease peptide β-amyloid atp-driven copper transport high-affinity transferrin receptor conserved iron-responsive elements ferroportin-mediated iron transport iron-export ferroxidase activity 2-amyloid precursor protein amyloid precursor protein iron-zinc interaction astrocyte-endothelial interactions transferrin-bound iron uptake duodenal iron-regulated transporter hepcidin-mediated internalization blood–brain barrier blood-brain-barrier hepcidin-induced endocytosis privacy choices/manage cookies cerebral amyloid angiopathy +-coupled fe2+ transport nramp2/dmt1 iron transporter brain barrier systems iron-regulated ferric reductase intestinal brush border major β-secretase iron regulatory protein-1 regulatory rna sequences x-ray structure beta-amyloid expression age-dependent uptake manganese-responsive protein γ-secretase activity divalent metal transporter intestinal iron transport full article pdf

Questions {❓}

Broersen K, Rousseau F, Schymkowitz J (2010) The culprit behind amyloid beta peptide related neurotoxicity in Alzheimer’s disease: oligomer size or conformation?
Garrick MD et al (2006) DMT1: which metals does it transport?

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      description: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.
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