Cu and Zn coordination to amyloid peptides: From fascinating chemistry to debated pathological relevance

Elena Atrián-Blasco (1) , Paulina Gonzalez (2) , Alice Santoro (2) , Bruno Alies (3) , Peter Faller (2) , Christelle Hureau (1)

1 LCC - Laboratoire de chimie de coordination
2 Institut de Chimie de Strasbourg
3 ChemBioPharm

Several diseases share misfolding of different peptides and proteins as a key feature for their development. This is the case of important neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and type II diabetes mellitus. Furthermore, metal ions such as copper and zinc might play an important role upon interaction with amyloidogenic peptides and proteins, which could impact their aggregation and toxicity abilities. In this review, the different coordination modes proposed for copper and zinc with amyloid-β, α-synuclein and IAPP will be reviewed as well as their impact on the aggregation, and ROS production in the case of copper. In addition, a special focus will be given to the mutations that affect metal binding and lead to familial cases of the diseases. Different modifications of the peptides that have been observed in vivo and could be relevant for the coordination of metal ions are also described.

Mots clés: Amyloid-β; α-synuclein; amylin; familial mutations; copper; zinc

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

Elena Atrián-Blasco, Paulina Gonzalez, Alice Santoro, Bruno Alies, Peter Faller, et al.. Cu and Zn coordination to amyloid peptides: From fascinating chemistry to debated pathological relevance. Coordination Chemistry Reviews, 2018, 371, pp.38-55. ⟨10.1016/j.ccr.2018.04.007⟩. ⟨hal-01858236⟩