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Membrane-targeted strategies for modulating APP and Aβ-mediated toxicity
Authors:Katherine A Price  Peter J Crouch  Paul S Donnelly  Colin L Masters  Anthony R White  Cyril C Curtain
Institution:Department of Pathology, The University of Melbourne, Victoria, Australia;The Mental Health Research Institute, Parkville, Victoria, Australia;Centre for Neuroscience, The University of Melbourne, Victoria, Australia;Bio21 Molecular Science and Biotechnology Institute, Parkville, Victoria, Australia;School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia;School of Physics, Monash University, Clayton, Victoria, Australia
Abstract:Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by numerous pathological features including the accumulation of neurotoxic amyloid-β (Aβ) peptide. There is currently no effective therapy for AD, but the development of therapeutic strategies that target the cell membrane is gaining increased interest. The amyloid precursor protein (APP) from which Aβ is formed is a membrane-bound protein, and Aβ production and toxicity are both membrane mediated events. This review describes the critical role of cell membranes in AD with particular emphasis on how the composition and structure of the membrane and its specialized regions may influence toxic or benign Aβ/APP pathways in AD. The putative role of copper (Cu) in AD is also discussed, and we highlight how targeting the cell membrane with Cu complexes has therapeutic potential in AD.
Keywords:amyloid  copper  membranes
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