Journal article
Mixed ligand Cu2 complexes of a model therapeutic with Alzheimer's amyloid-β peptide and monoamine neurotransmitters
VB Kenche, I Zawisza, CL Masters, W Bal, KJ Barnham, SC Drew
Inorganic Chemistry | Published : 2013
DOI: 10.1021/ic302289r
Abstract
8-Hydroxyquinolines (8HQ) have found widespread application in chemistry and biology due to their ability to complex a range of transition metal ions. The family of 2-substituted 8HQs has been proposed for use in the treatment of Alzheimer's disease (AD). Most notably, the therapeutic PBT2 (Prana Biotechnology Ltd.) has been shown to act as an efficient metal chaperone, disaggregate metal-enriched amyloid plaques comprised of the Aβ peptide, inhibit Cu/Aβ redox chemistry, and reverse the AD phenotype in transgenic animal models. Yet surprisingly little is known about the molecular interactions at play. In this study, we show that the homologous ligand 2-[(dimethylamino) methyl]-8-hydroxyquin..
View full abstractGrants
Funding Acknowledgements
This work was supported by a Future Fellowship (S.C.D.) administered by the Australian Research Council and a Program Grant administered by the National Health and Medical Research Council of Australia (K.J.B., C.L.M). K.J.B. is an NHMRC Senior Research Fellow. Peptide synthesis was carried out by John Karas in the Peptide Technology Facility of the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne. The alpha-synuclein protein was kindly provided by Roberto Cappai, The University of Melbourne. The potentiometric equipment used was sponsored by the Centre for Preclinical Research and Technology (CePT), a project cosponsored by European Regional Development Fund and Innovative Economy, The National Cohesion Strategy of Poland.