Journal article
Selective intracellular release of copper and zinc ions from bis( thiosemicarbazonato) complexes reduces levels of Alzheimer disease amyloid-beta peptide
Paul S Donnelly, Aphrodite Caragounis, Tai Du, Katrina M Laughton, Irene Volitakis, Robert A Cherny, Robyn A Sharples, Andrew F Hill, Qiao-Xin Li, Colin L Masters, Kevin J Barnham, Anthony R White
JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2008
Abstract
Copper and zinc play important roles in Alzheimer disease pathology with recent reports describing potential therapeutics based on modulation of metal bioavailability. We examined the ability of a range of metal bis(thiosemicarbazonato) complexes (MII(btsc), where M=CuII or ZnII) to increase intracellular metal levels in Chinese hamster ovary cells overexpressing amyloid precursor protein (APP-CHO) and the subsequent effect on extracellular levels of amyloid-beta peptide (Abeta). The CuII(btsc) complexes were engineered to be either stable to both a change in oxidation state and dissociation of metal or susceptible to intracellular reduction and dissociation of metal. Treatment of APP-CHO ce..
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