Topics of research
Theme 1 : Molecular basis of metal ions – amyloids interaction
Principal investigator: C. Hureau
We study the coordination of Cu(I/II) and Zn(II) with the amyloid-β peptide involved in Alzheimer’s disease and how it could impact the two deleterious processes at the origin of the pathology, i.e. oxidative stress and peptide assembly. A possible synergetic link between the two processes is also under investigation.
Theme 2 : Development of new therapeutic approaches
Principal investigator: C. Esmieu & C. Hureau
Three main strategies are under focus.
The first one is centered on the design of chelating compounds able to remove Cu from the amyloid-β. Various strategies are investigated: chelation of Cu(I) or/and Cu(II), impact of Zn(II) in Cu extraction from amyloid-β by chelators, importance of kinetics in Cu detoxification process, traceable chelation, use of metallated pro-drug as less-toxic surrogate of the chelators, chelation with additional abilities: artificial secretase, modulators of the assembly…
The second one relies on the use of natural and artificial chaperones, id est (bio-)molecules able to modulate the amyloid-β assembly process. Artificial chaperones include Re–based compounds, polyoxometallates, porphyrines, or Ln-complexes.
The third one aims at designing and investigating new (in vitro and in vivo) imaging tools to monitor the assembly process of the amyloid-β peptide and of other amyloid-forming peptides.
Theme 3: Artificial Lanthanide Enzymes
Principal investigator: E. Mathieu
This project focuses on developing artificial lanthanide enzymes as models of lanthanide methanol dehydrogenases. We aim to deepen our understanding of the interactions between lanthanide ions and peptides, as well as the role played by the metal ion in the catalytic activity of the enzyme