Metal-binding to Amyloid-β Peptide: Coordination, Aggregation and Reactive Oxygen Species Production

Melisa del Barrio (1, 2, 3) , Valentina Borghesani (1, 2, 3) , Christelle Hureau (1, 2, 3) , Peter Faller (4)

1 LCC - Laboratoire de chimie de coordination
2 Toulouse INP - Institut National Polytechnique (Toulouse)
3 UT3 - Université Toulouse III - Paul Sabatier
4 Institut de Chimie de Strasbourg

Amyloid-plaques are a hallmark of Alzheimer’s disease. They consist mainly of an aggregated peptide called amyloid-β. These plaques also accumulate high concentrations of metal ions, mainly Cu, Zn and Fe. Cu and Zn directly bind to amyloid-β in vivo. This triggered a strong research activity in order to understand the biology and chemistry of the interaction between metal ions and amyloid-β. This includes also the chemical and biophysical aspects of the metal-amyloid-β complexes. The present article describes the coordination chemistry of the Cu(II), Cu(I), Zn(II) and Fe(II) complexes in terms of ligand spheres and affinities. Moreover, metal ions modulate the selfassembly of amyloid-β into amyloids, a central event in Alzheimer’s disease. Attention was paid on the catalytic role of Cu-bound to amyloid-β, in particular in terms of the production of reactive oxygen species, which have been proposed to be involved in the disease progression. Recent mechanistic insights are described.

Domaines: Neurobiologie; Biochimie [q-bio.BM]; Chimie de coordination

Melisa del Barrio, Valentina Borghesani, Christelle Hureau, Peter Faller. Metal-binding to Amyloid-β Peptide: Coordination, Aggregation and Reactive Oxygen Species Production. Anthony White; Michael Aschner; Lucio Costa; Ashley Bush. Biometals in Neurodegenerative Diseases 1st Edition - Mechanisms and Therapeutics, Elsevier, 2017, 9780128045626. ⟨hal-01635566⟩