The role of iron and copper in the aetiology of neurodegenerative disorders - Therapeutic implications

被引:106
作者
Perry, G [1 ]
Sayre, LM [1 ]
Atwood, CS [1 ]
Castellani, RJ [1 ]
Cash, AD [1 ]
Rottkamp, CA [1 ]
Smith, MA [1 ]
机构
[1] Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA
关键词
D O I
10.2165/00023210-200216050-00006
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Abnormalities in the metabolism of the transition metals iron and copper have been demonstrated to play a crucial role in the pathogenesis of various neurodegenerative diseases. Metal homeostasis as it pertains to alterations in brain function in neurodegenerative diseases is reviewed in this article in depth, While there is documented evidence for alterations in the homeostasis, redox-activity and localisation of transition metals, it is also important to realise that alterations in specific copper- and iron-containing metalloenzymes appear to play a crucial role in the neurodegenerative process. These changes provide the opportunity to identify pathways where modification of the disease process can occur, potentially offering opportunities for clinical intervention. As understanding of disease aetiology evolves, so do the tools with which diseases are treated. In this article, we examine not only the possible mechanism of disease but also how pharmaceuticals may intervene, from direct and indirect antioxidant therapy to strategies involving gene therapy.
引用
收藏
页码:339 / 352
页数:14
相关论文
共 120 条
[1]  
Andrus PK, 1998, J NEUROCHEM, V71, P2041
[2]   Dramatic aggregation of Alzheimer Aβ by Cu(II) is induced by conditions representing physiological acidosis [J].
Atwood, CS ;
Moir, RD ;
Huang, XD ;
Scarpa, RC ;
Bacarra, NME ;
Romano, DM ;
Hartshorn, MK ;
Tanzi, RE ;
Bush, AI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (21) :12817-12826
[3]  
BENSHACHAR D, 1993, PROG NEURO-PSYCHOPH, V17, P139
[4]  
Bogdanov MB, 1998, J NEUROCHEM, V71, P1321
[5]   Promotion of transition metal-induced reactive oxygen species formation by β-amyloid [J].
Bondy, SC ;
Guo-Ross, SX ;
Truong, AT .
BRAIN RESEARCH, 1998, 799 (01) :91-96
[6]   Pharmacological treatment of cognitive deficits in Alzheimer's disease [J].
Brodaty, H ;
Ames, D ;
Boundy, KL ;
Hecker, J ;
Snowdon, J ;
Storey, E ;
Yates, MW .
MEDICAL JOURNAL OF AUSTRALIA, 2001, 175 (06) :324-329
[7]   Consequences of manganese replacement of copper for prion protein function and proteinase resistance [J].
Brown, DR ;
Hafiz, F ;
Glasssmith, LL ;
Wong, BS ;
Jones, IM ;
Clive, C ;
Haswell, SJ .
EMBO JOURNAL, 2000, 19 (06) :1180-1186
[8]   Spongiform encephalopathies - B lymphocytes and neuroinvasion [J].
Brown, P .
NATURE, 1997, 390 (6661) :662-663
[9]  
Brown DR, 1998, J NEUROCHEM, V70, P1686
[10]   Normal prion protein has an activity like that of superoxide dismutase [J].
Brown, DR ;
Wong, BS ;
Hafiz, F ;
Clive, C ;
Haswell, SJ ;
Jones, IM .
BIOCHEMICAL JOURNAL, 1999, 344 :1-5