Research reportIron and transferrrin uptake by brain and cerebrospinal fluid in the rat
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Restoration of metal homeostasis: a potential strategy against neurodegenerative diseases
2023, Ageing Research ReviewsRole of endolysosome function in iron metabolism and brain carcinogenesis
2021, Seminars in Cancer BiologyCitation Excerpt :Despite the presence of iron binding proteins and export systems, incubation of cells with Fe3+ results in increases in the intracellular labile iron pool and oxidative damage [105,106]. While most cells can regulate levels of iron by cell division, neurons are post-mitotic cells and must rely on iron homeostatic mechanisms to avoid iron-induced oxidative stress [105], including downregulating the expression of TfR [107,108]. Neurons can also control levels of iron at the molecular level via post-transcriptional modification by iron regulatory proteins (IRP1 and IRP2).
Designing peptide nanoparticles for efficient brain delivery
2020, Advanced Drug Delivery ReviewsCitation Excerpt :A cognate ligand for the TfR is the iron binding protein Tf, which is a transmembrane glycoprotein consisting of two 90 kDa subunits, linked by intermolecular disulfide bonds and with each subunit binding to one molecule of Tf [183]. Although Tf is a specific ligand to TfR, Tf is a questionable targeting moiety for drug delivery, mainly due to the fact that only a small amount of Tf is transcytosed across the BECs [184,185]. Thus, monoclonal antibodies against the TfR, which bind to epitopes on the extracellular domain of TfR distal to the Tf binding side circumventing competition with endogenous Tf, have been widely developed for RMT-based delivery [186,187].
Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration
2019, Free Radical Biology and MedicineCitation Excerpt :This model is supported by the observation that cultured bovine BCECs cycle Tf-TfR1 complexes and that holo-Tf transported across these cells may not undergo intraendothelial degradation [47,174]. However no evidence has emerged to demonstrate the transport of Tf from the systemic circulation across BCECs into the brain [43,150,202]. Astrocytes are essential support cells in the neurovascular unit and serve to release the iron supplied by BCECs to the neurons while mitigating iron toxicity [1,23].
Regulatory mechanisms for iron transport across the blood-brain barrier
2017, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The identification of the mechanism by which apo-Tf induces iron release from endothelial cells, that may involve synergistic interaction with hepcidin, is perhaps the critical step to understanding regional control of brain iron uptake. In conclusion, these data not only provide further support for a DMT1-dependent endocytic process mediating the passage of iron across the endothelial cells that constitute the BBB but addresses a long-observed enigma in the field; namely, the disproportionately greater transport of iron relative to Tf into the brain [24,26,27,38,42–45]. We propose that the levels of apo-Tf and iron delivered to the brain are tightly regulated by the ratio of apo-Tf:holo-Tf in conjunction with hepcidin in the extracellular fluid of each brain region.