Current status of metals as therapeutic targets in Alzheimer's disease

被引：172

作者：

Finefrock, AE

Bush, AI

Doraiswamy, PM

机构：

[1] Duke Univ, Med Ctr, Dept Psychiat, Div Biol Psychiat, Durham, NC 27710 USA

[2] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol Genet, Charlestown, MA USA

[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Aging Unit, Charlestown, MA USA

[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA

[5] Duke Univ, Med Ctr, Dept Geriatr Med, Durham, NC USA

[6] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA

来源：

JOURNAL OF THE AMERICAN GERIATRICS SOCIETY | 2003年 / 51卷 / 08期

关键词：

Alzheimer's disease; clioquinol; copper; zinc; beta-amyloid;

D O I：

10.1046/j.1532-5415.2003.51368.x

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

There is accumulating evidence that interactions between beta-amyloid and copper, iron, and zinc are associated with the pathophysiology of Alzheimer's disease (AD). A significant dyshomeostasis of copper, iron, and zinc has been detected, and the mismanagement of these metals induces beta-amyloid precipitation and neurotoxicity. Chelating agents offer a potential therapeutic solution to the neurotoxicity induced by copper and iron dyshomeostasis. Currently, the copper and zinc chelating agent clioquinol represents a potential therapeutic route that may not only inhibit beta-amyloid neurotoxicity, but may also reverse the accumulation of neocortical beta-amyloid. A Phase II double-blind clinical trial of clioquinol with B-12 supplementation will be published soon, and the results are promising. This article summarizes the role of transition metals in amyloidgenesis and reviews the potential promise of chelation therapy as a treatment for AD.

引用

页码：1143 / 1148

页数：6

共 43 条

[31] Metalloenzyme-like activity of Alzheimer's disease β-amyloid -: Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2 [J].