Therapeutic treatments for Alzheimer's disease based on metal bioavailability.
The amyloid beta peptide (Abeta) has been widely implicated as a significant causative agent in Alzheimer's disease, although the common mechanistic links between Abeta and other critical elements of Alzheimer's disease, such as advancing age and oxidative stress, are still poorly understood. Here we review data indicating that biometal dyshomeostasis plays a role in these aspects of Alzheimer's disease. Although strong evidence has been published demonstrating a role for iron and zinc in Alzheimer's disease, we have here limited our discussion to data on the role of copper. We also describe how the development of therapeutic agents designed to modulate metal bioavailability has provided promising results in the treatment of Alzheimer's disease. The metal ligand clioquinol has been used successfully in vitro, as well as in animal models and small clinical trials, and a new generation of metal ligand-based therapeutics is under development.
Crouch
Peter J
PJ
Department of Pathology, University of Melbourne, Victoria 3010, Australia.
Barnham
Kevin J
KJ
Bush
Ashley I
AI
White
Anthony R
AR
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007464:Clioquinol / Q000494:pharmacology / Q000627:therapeutic use*; D003300:Copper / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D011485:Protein Binding; D014131:Trace Elements / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D018697:Nootropic Agents; D014131:Trace Elements; D003300:Copper; D007464:Clioquinol