A shortjourney into the role of metal ions in Alzheimer’s disease.
Esmieu Charlène,aEmilie Mathieu,a Geneviève Pratviel and Christelle Hureau.a,*
Laboratoire de Chimie de Coordination, 205 Route deNarbonne, 31077 Toulouse cedex04, France
Alzheimer (AD) is a multifactorial pathologywhere two key events have been linked to the etiology of the disease: (i) theself-assembly process of the Alzheimer-related amyloid-β (Aβ) peptides leading to the deposits of Aβ amyloids inthe senile plaques detected in AD patients  and (ii) oxidativestress. Metal ions (mainly copper andzinc) have been found in the senile plaques in abnormally high level. They canmodulate the self-assembly of the Aβ peptides and Aβ-bound copper ions can catalyze the production of Reactive OxygenSpecies. They are thus key players in the pathology.
During the talk, I will give an overview of theapproaches we have developed in the last years to (i) first understand at themolecular level how metal ions are linked to the fate of the disease in connectionwith the modulation of Aβ self-assembly and with Aβ-bound Cu-induced ROS production [1-3] and to (ii) overcome theirdeleterious effects by new copper-targeting molecules,[3-5] or inorganicchaperons of the Aβ self-assembly.
1. Atrian-Blasco, E.; Gonzalez, P.;Santoro, A.; Alies, B.; Faller, P.; Hureau, C., Cu and Zn coordination toamyloids: a chemistry of pathological importance ? Coord. Chem. Rev. 2018, 371, 38-55.
2. Cheignon, C.; Tomas, M.;Bonnefont-Rousselot, D.; Faller, P.; Hureau, C.; Collin, F., Oxidative stressand the amyloid beta peptide in Alzheimer’s Disease. Redox Biology 2018, 14, 450-464.
3. Esmieu, C.; Guettas, D.;Conte-Daban, et al., Copper-Targeting Approaches in Alzheimer’s Disease: How ToImprove the Fallouts Obtained from in Vitro Studies. Inorg. Chem. 2019, 58, 13509-13527.
4. M. Okafor, P. Gonzalez, P. Ronot, et al. Development of Cu(II)-specific peptideshuttles capable of preventing Cu–amyloid-β toxicity and importing bioavailable Cuinto cells. Chem. Sci. 2022, 13, 11829-40
5. E.Atrian-Blasco, L. De Cremoux, X. Lin, R. Mitchell-Heggs, L. Sabater, S.Blanchard and C. Hureau. Keggin-typePolyoxometalates as Cu(II) chelators in the context of Alzheimer’s disease, Chem. Commun., 2022, 58, 2367-70.