Interbio aims at promoting interdisciplinary and interregional research in the field of health & life sciences. Interbio can provide mobility support (transport & accommodation) for scientists interested in setting up collaborative research projects. For more information, please contact your local WP3 coordinator.
Structural and functional aspects of the Cu/Fe-amyloid-beta complex
Perspectives of extension of this common project to a more ambitious proposal to be submitted to funding agencies : Long term Added value of the cooperation : Exchange of expertise
Summary of the proposal : Background: There is a large body of evidence that metal ions play a role in Alzheimer's disease (AD). This includes the essential metal ions iron, zinc and copper. Their involvement is supported, among other evidence, by their accumulation in the amyloid plaques, a hallmark of AD made of aggregated Abeta. Cu (and Fe) ions are thought to bind to Abeta under AD conditions and to be involved in two key steps of AD, the aggregation of the peptide Abeta into amyloid plaques (a hallmark of AD) and ii) in the production of reactive oxygen species (ROS) leading to neuronal death.
Aims: The general goal is to better understand the interaction of Cu (and Fe) ions with Abeta, and the consequence on aggregation and ROS production. The more specific aims are therefore: i) to evaluate the capability of Cu-Abeta (and Fe-Abeta) to produce superoxide and peroxide in the presence of a physiological reductant (ascorbate, GSH etc) and molecular oxygen by the test established by the Gomes group, and ii) to study the role of metal ions on aggregation and stability of Abeta by FTIR and other biophysical techniques.
Complementary of the partners:The group if P. Faller in Toulouse has a long standing experience in the structural and functional studies on the interaction of the peptide Abeta with metal ions by different methods. The group of C. Gomes has strong experience in protein stability and several biophysical methods, in particular in FTIR. Moreover he established a new assay for measuring superoxide and hydrogen peroxide via specific enzymes. So the groups are complementary and the application of the methods and techniques connected with the protein stability and folding know how by the Gomes group will fit very well for application to the Abeta-metal ion system of the Faller group.
Antonio PINEDA-LUCENA, Valencia Claudio GOMES, Lisboa
Using metabonomics to understand fatty acid oxidation disease