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
[61]   Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice [J].
Nagano, S ;
Ogawa, Y ;
Yanagihara, T ;
Sakoda, S .
NEUROSCIENCE LETTERS, 1999, 265 (03) :159-162
[62]   New reaction pathways of dopamine under oxidative stress conditions: Nonenzymatic iron-assisted conversion to norepinephrine and the neurotoxins 6-hydroxydopamine and 6,7-dihydroxytetrahydroisoquinoline [J].
Napolitano, A ;
Pezzella, A ;
Prota, G .
CHEMICAL RESEARCH IN TOXICOLOGY, 1999, 12 (11) :1090-1097
[63]   Neuronal oxidative stress precedes amyloid-β deposition in Down syndrome [J].
Nunomura, A ;
Perry, G ;
Pappolla, MA ;
Friedland, RP ;
Hirai, K ;
Chiba, S ;
Smith, MA .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (11) :1011-1017
[64]  
Nunomura A, 1999, J NEUROSCI, V19, P1959
[65]   Oxidative damage is the earliest event in Alzheimer disease [J].
Nunomura, A ;
Perry, G ;
Aliev, G ;
Hirai, K ;
Takeda, A ;
Balraj, EK ;
Jones, PK ;
Ghanbari, H ;
Wataya, T ;
Shimohama, S ;
Chiba, S ;
Atwood, CS ;
Petersen, RB ;
Smith, MA .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2001, 60 (08) :759-767
[66]  
NUNOMURA A, 2000, BRAIN PATHOL, V10, P783
[67]   Lipoperoxidation is selectively involved in progressive supranuclear palsy [J].
Odetti, P ;
Garibaldi, S ;
Norese, R ;
Angelini, G ;
Marinelli, L ;
Valentini, S ;
Menini, S ;
Traverso, N ;
Zaccheo, D ;
Siedlak, S ;
Perry, G ;
Smith, MA ;
Tabaton, M .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (05) :393-397
[68]   Copper(II)-induced self-oligomerization of α-synuclein [J].
Paik, SR ;
Shin, HJ ;
Lee, JH ;
Chang, CS ;
Kim, J .
BIOCHEMICAL JOURNAL, 1999, 340 :821-828
[69]  
Pappolla MA, 1998, AM J PATHOL, V152, P871
[70]   Copper stimulates endocytosis of the prion protein [J].
Pauly, PC ;
Harris, DA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (50) :33107-33110