Acrolein and Copper as Competitive Effectors of α‐Synuclein

en

2019-12-05

0947-6539

Chemistry – A European Journal

Mounting evidence supports the role of amyloidogenesis, oxidative stress, and metal dyshomeostasis in the development of neurodegenerative disorders. Parkinson's Disease is characterized by α-synuclein (αSyn) accumulation and aggregation in brain Show moreMounting evidence supports the role of amyloidogenesis, oxidative stress, and metal dyshomeostasis in the development of neurodegenerative disorders. Parkinson's Disease is characterized by α-synuclein (αSyn) accumulation and aggregation in brain regions, also promoted by Cu2+ . αSyn is modified by reactive carbonyl species, including acrolein (ACR). Notwithstanding these findings, the interplay between ACR, copper, and αSyn has never been investigated. Therefore, we explored more thoroughly the effects of ACR on αSyn using an approach based on LC-MS/MS analysis. We also evaluated the influence of Cu2+ on the protein carbonylation and how the ACR modification impacts the Cu2+ binding and the production of Reactive Oxygen Species (ROS). Finally, we investigated the effects of ACR and Cu2+ ions on the αSyn aggregation by dynamic light scattering and fluorescence assays. Cu2+ regioselectively inhibits the modification of His50 by ACR, the carbonylation lowers the affinity of His50 for Cu2+ and ACR inhibits αSyn aggregation both in the presence and in the absence of Cu2+. Show less

Chem. Eur. J.

ACL

Chimie/Chimie inorganique

Dipartimento di Scienze ChimicheUniversità degli Studi di Catania A. Doria 6 95125 Catania Italy
Istituto di CristallografiaConsiglio Nazionale delle Ricerche P. Gaifami 18 95126 Catania Italy

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