Membrane-targeted strategies for modulating APP and Abeta-mediated toxicity.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by numerous pathological features including the accumulation of neurotoxic amyloid-beta (Abeta) 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 Abeta is formed is a membrane-bound protein, and Abeta 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 Abeta/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.
Price
Katherine A
KA
Department of Pathology, The University of Melbourne, Victoria, Australia. k.price@pgrad.unimelb.edu.au
Crouch
Peter J
PJ
Donnelly
Paul S
PS
Masters
Colin L
CL
White
Anthony R
AR
Curtain
Cyril C
CC
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D003300:Copper / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008563:Membrane Lipids; D008565:Membrane Proteins; D003300:Copper