Open AccessMembrane‐targeted strategies for modulating APP and Aβ‐mediated toxicity
Author(s) -
Price Katherine A.,
Crouch Peter J.,
Donnelly Paul S.,
Masters Colin L.,
White Anthony R.,
Curtain Cyril C.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00642.x
Subject(s) - membrane , amyloid precursor protein , cell , cell membrane , microbiology and biotechnology , p3 peptide , membrane protein , chemistry , alzheimer's disease , biology , biochemistry , medicine , disease , pathology
• Introduction • Role of amyloid‐β (Aβ) and APP in AD • Cell membranes ‐ The microstructure of cell membranes• Aβ and cell membranes ‐ APP processing and its relationship with specialized membrane regions ‐ Aβ Interactions with the cell membrane ‐ Cu 2+ and the formation of the toxic species ‐ Membrane composition, morphology and Aβ aggregation ‐ Membrane composition and conformation and the relationship with Cu• AD therapeutics targeting the membrane ‐ AD therapeutics targeting membrane receptors• Potential for metal complex delivered metal ions to alter membrane‐mediated activation pathways • ConclusionsAbstract 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.