The modulation of metal bio-availability as a therapeutic strategy for the treatment of Alzheimer's disease.
The postmortem Alzheimer's disease brain is characterized histochemically by the presence of extracellular amyloid plaques and neurofibrillary tangles. Also consistent with the disease is evidence for chronic oxidative damage within the brain. Considerable research data indicates that these three critical aspects of Alzheimer's disease are interdependent, raising the possibility that they share some commonality with respect to the ever elusive initial factor(s) that triggers the development of Alzheimer's disease. Here, we discuss reports that show a loss of metal homeostasis is also an important event in Alzheimer's disease, and we identify how metal dyshomeostasis may contribute to development of the amyloid-beta, tau and oxidative stress biology of Alzheimer's disease. We propose that therapeutic agents designed to modulate metal bio-availability have the potential to ameliorate several of the dysfunctional events characteristic of Alzheimer's disease. Metal-based therapeutics have already provided promising results for the treatment of Alzheimer's disease, and new generations of pharmaceuticals are being developed. In this review, we focus on copper dyshomeostasis in Alzheimer's disease, but we also discuss zinc and iron.
Crouch
Peter J
PJ
Department of Pathology and Centre for Neuroscience, The University of Melbourne, Australia.
White
Anthony R
AR
Bush
Ashley I
AI
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D006801:Humans; D008670:Metals / Q000378:metabolism*; D018384:Oxidative Stress; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008670:Metals; D016875:tau Proteins