Brain iron metabolism: neurobiology and neurochemistry |
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Authors: | Ke Ya Qian Zhong Ming |
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Affiliation: | Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, NT, Hong Kong. |
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Abstract: | New findings obtained during the past years, especially the discovery of mutations in the genes associated with brain iron metabolism, have provided key insights into the homeostatic mechanisms of brain iron metabolism and the pathological mechanisms responsible for neurodegenerative diseases. The accumulated evidence demonstrates that misregulation in brain iron metabolism is one of the initial causes for neuronal death in some neurodegenerative disorders. The errors in brain iron metabolism found in these disorders have a multifactorial pathogenesis, including genetic and nongenetic factors. The disturbances of iron metabolism might occur at multiple levels, including iron uptake and release, storage, intracellular metabolism and regulation. It is the increased brain iron that triggers a cascade of deleterious events, leading to neuronal death in these diseases. In the article, the recent advances in studies on neurochemistry and neuropathophysiology of brain iron metabolism were reviewed. |
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Keywords: | AD, Alzheimer's disease BBB, blood–brain barrier CNS, central nervous system CP, ceruloplasmin CSF, cerebrospinal fluid Dcytb, duodenal cytochrome b DMT1, divalent metal transporter 1 (previously referred to as Nramp2 or DCT1) FLP, ferritin light polypeptide FP1, ferroportin 1 HFE, hemochromatosis protein (the protein mutated in hereditary hemochromatosis) HO-1, heme oxygenase-1 Hp, Hephaestin HSS, Hallerorden–Spatz syndrome IF, interstitial fluid IRE, iron responsive element IRP, iron regulatory protein Lf, lactoferrin or lactotransferrin LfR, lactoferrin receptor MTf, melanotransferrin NTBI, non-transferrin-bound iron PANK2, a novel pantothenate kinase gene PD, Parkinson's disease ROS, reactive oxygen species SDR2, stromal cell-derived receptor2 sMTf, a soluble form of melanotransferrin TCT, trivalent cation-specific transporter Tf-Fe, transferrin-bound iron Tf/TfR, transferrin/transferrin receptor |
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