Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 72, Issue 4, Pages 709-727Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-014-1771-4
Keywords
Iron; Blood-brain barrier; Astrocytes; Transferrin; Amyloid precursor protein
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Funding
- NIDDK NIH HHS [R01 DK077826, R01 DK053820] Funding Source: Medline
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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-beta 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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