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Brain iron metabolism: neurobiology and neurochemistry
Authors:Ke Ya  Qian Zhong Ming
Affiliation:Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, NT, Hong Kong.
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.
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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