tailieunhanh - Báo cáo khoa học: 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 crit-ical 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 | ỊFEBS Journal MINIREVIEW The modulation of metal bio-availability as a therapeutic strategy for the treatment of Alzheimer s disease Peter J. Crouch1 Anthony R. White1 and Ashley I. Bush2 3 1 Department of Pathology and Centre for Neuroscience The University of Melbourne Australia 2 The MentalHealth Research Institute of Victoria Parkville Australia 3 Department of Psychiatry Massachusetts General Hospital Charlestown MA USA Keywords Alzheimer s disease amyloid-b biometals copper iron oxidative stress tau zinc Correspondence A. I. Bush The MentalHealth Research Institute of Victoria 155 Oak Street Parkville Victoria 3052 Australia Fax 61 39387 5061 Tel 61 39389 2962 E-mail abush@ Received 9 March 2007 revised 17 May 2007 accepted 18 May 2007 doi 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-b 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