Iron misregulation in the brain: a primary cause of neurodegenerative disorders

被引:303
作者
Ke, Y
Qian, ZM [1 ]
机构
[1] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Lab Brain Iron Metab, Kowloon, Hong Kong, Peoples R China
[2] Hebei Normal Univ, Inst Neurobiol & Neuropharmacol, Shijiazhuang, Hebei Province, Peoples R China
关键词
D O I
10.1016/S1474-4422(03)00353-3
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
High iron concentrations in the brains of patients and the discovery of mutations in the genes associated with iron metabolism in the brain suggest that iron misregulation in the brain plays a part in neuronal death in some neuro-degenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases and Hallervorden-Spatz syndrome. Iron misregulation in the brain may have genetic and non-genetic causes. The disrupted expression or function of proteins involved in iron metabolism increases the concentration of iron in the brain. Disturbances can happen at any of several stages in iron metabolism (including uptake and release, storage, intracellular metabolism, and regulation). Increased brain iron triggers a cascade of deleterious events that lead to neurodegeneration. An understanding of the process of iron reglation in the brain, the proteins important in this process, and the effects of iron misregulation could help to treat or prevent neurodegenerative disrders.
引用
收藏
页码:246 / 253
页数:8
相关论文
共 104 条
[71]   Hepcidin, a urinary antimicrobial peptide synthesized in the liver [J].
Park, CH ;
Valore, EV ;
Waring, AJ ;
Ganz, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (11) :7806-7810
[72]   The role of iron and copper in the aetiology of neurodegenerative disorders - Therapeutic implications [J].
Perry, G ;
Sayre, LM ;
Atwood, CS ;
Castellani, RJ ;
Cash, AD ;
Rottkamp, CA ;
Smith, MA .
CNS DRUGS, 2002, 16 (05) :339-352
[73]   HALLERVORDEN-SPATZ DISEASE - CYSTEINE ACCUMULATION AND CYSTEINE DIOXYGENASE DEFICIENCY IN THE GLOBUS PALLIDUS [J].
PERRY, TL ;
NORMAN, MG ;
YONG, VW ;
WHITING, S ;
CRICHTON, JU ;
HANSEN, S ;
KISH, SJ .
ANNALS OF NEUROLOGY, 1985, 18 (04) :482-489
[74]  
Piñero DJ, 2000, CELL MOL BIOL, V46, P761
[75]   Domain homologues of dopamine β-hydroxylase and ferric reductase:: roles for iron metabolism in neurodegenerative disorders? [J].
Ponting, CP .
HUMAN MOLECULAR GENETICS, 2001, 10 (17) :1853-1858
[76]   Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway [J].
Qian, ZM ;
Li, HY ;
Sun, HZ ;
Ho, K .
PHARMACOLOGICAL REVIEWS, 2002, 54 (04) :561-587
[77]   Ceruloplasmin promotes iron uptake rather than release in BT325 cells [J].
Qian, ZM ;
Tsoi, YK ;
Ke, Y ;
Wong, MS .
EXPERIMENTAL BRAIN RESEARCH, 2001, 140 (03) :369-374
[78]   Expression of iron transport proteins and excessive iron accumulation in the brain in neurodegenerative disorders [J].
Qian, ZM ;
Wang, Q .
BRAIN RESEARCH REVIEWS, 1998, 27 (03) :257-267
[79]   Brain iron transport and neurodegeneration [J].
Qian, ZM ;
Shen, X .
TRENDS IN MOLECULAR MEDICINE, 2001, 7 (03) :103-108
[80]   Rethinking the role of ceruloplasmin in brain iron metabolism [J].
Qian, ZM ;
Ke, Y .
BRAIN RESEARCH REVIEWS, 2001, 35 (03) :287-294