The risks of free copper in the body and the development of useful anticopper drugs

被引:65
作者
Brewer, George J. [1 ,2 ]
机构
[1] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI USA
[2] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA
关键词
Alzheimer's disease; free copper; tetrathiomolybdate; Wilson's disease;
D O I
10.1097/MCO.0b013e328314b678
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Purpose of review To review the toxicity and risks of free copper in Wilson's disease, Alzheimer's disease, other disease of neurodegeneration, and cognitive loss in the general population. We will also review the anticopper drugs and how lowering free copper levels with an anticopper drug inhibits fibrosis, inflammation, and autoimmunity. Recent findings Some exciting recent work indicates that free copper levels are increased in Alzheimer's disease, and copper may be involved in disease pathogenesis, opening the way to possible therapy of Alzheimer's disease with anticopper drugs. Copper may also be involved in other diseases of neurodegeneration. A very exciting recent study indicts high intake of copper, mostly from copper supplements, in conjunction with a high-fat diet in more rapid cognitive decline in the general population. Other data indicate that even low levels of copper in drinking water, perhaps similar to copper supplements, bypasses the liver, enters the circulation, increases the blood-brain penetration of copper, and may cause damage. Summary Some of the implications are that Alzheimer's disease and other diseases of neurodegeneration and fibrotic, inflammatory, and autoimmune diseases may be treatable by lowering the availability of free copper. People in the general population may wish to take steps to lower their free copper levels and, in particular, to abstain from taking copper supplements and ingesting significant amounts of copper in drinking water.
引用
收藏
页码:727 / 732
页数:6
相关论文
共 51 条
[1]
BACE1 cytoplasmic domain interacts with the copper chaperone for superoxide dismutase-1 and binds copper [J].
Angeletti, B ;
Waldron, KJ ;
Freeman, KB ;
Bawagan, H ;
Hussain, I ;
Miller, CCJ ;
Lau, KF ;
Tennant, ME ;
Dennison, C ;
Robinson, NJ ;
Dingwall, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (18) :17930-17937
[2]
[Anonymous], ANN M SOC NEUR SAN D
[3]
Tetrathiomolybdate therapy protects against concanavalin A and carbon tetrachloride hepatic damage in mice [J].
Askari, FK ;
Dick, R ;
Mao, M ;
Brewer, GJ .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2004, 229 (08) :857-863
[4]
The use of tetrathiomolybdate in treating fibrotic, inflammatory, and autoimmune diseases, including the non-obese diabetic mouse model [J].
Brewer, George J. ;
Dick, Robert ;
Zeng, Chunhua ;
Hou, Guoqing .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2006, 100 (5-6) :927-930
[5]
Recognition, diagnosis, and management of Wilson's disease [J].
Brewer, GJ .
PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE, 2000, 223 (01) :39-46
[6]
Treatment of Wilson disease with ammonium tetrathiomolybdate - IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease [J].
Brewer, GJ ;
Askari, F ;
Lorincz, MT ;
Carlson, M ;
Schilsky, M ;
Kluin, KJ ;
Hedera, P ;
Moretti, P ;
Fink, MK ;
Tankanow, R ;
Dick, RB ;
Sitterly, J .
ARCHIVES OF NEUROLOGY, 2006, 63 (04) :521-527
[7]
Brewer GJ, 2000, CLIN CANCER RES, V6, P1
[8]
Treatment of Wilson's disease with zinc. XVII: Treatment during pregnancy [J].
Brewer, GJ ;
Johnson, VD ;
Dick, RD ;
Hedera, P ;
Fink, JK ;
Kluin, KJ .
HEPATOLOGY, 2000, 31 (02) :364-370
[9]
WILSON DISEASE [J].
BREWER, GJ ;
YUZBASIYANGURKAN, V .
MEDICINE, 1992, 71 (03) :139-164
[10]
Treatment of Wilson's disease with zinc: XV - Long-term follow-up studies [J].
Brewer, GJ ;
Dick, RD ;
Johnson, VD ;
Brunberg, JA ;
Kluin, KJ ;
Fink, JK .
JOURNAL OF LABORATORY AND CLINICAL MEDICINE, 1998, 132 (04) :264-278