title: Current status of metals as therapeutic targets in Alzheimer's disease.
abstract: 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 B12 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.
authors.affiliation: Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Finefrock
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: P Murali
authors.initials: PM
authors.lastname: Doraiswamy
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D007464:Clioquinol / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004032:Diet; D006801:Humans; D007501:Iron / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D003300:Copper; D007464:Clioquinol; D007501:Iron; D003676:Deferoxamine; D015032:Zinc