Dataset Information

Differential effects of Cu2+ and Fe3+ ions on in vitro amyloid formation of biologically-relevant ?-synuclein variants.

ABSTRACT: Alterations in metal ion homeostasis appear coupled to neurodegenerative disorders but mechanisms are unknown. Amyloid formation of the protein ?-synuclein in brain cells is a hallmark of Parkinson's disease. ?-Synuclein can bind several metal ions in vitro and such interactions may affect the assembly process. Here we used biophysical methods to study the effects of micromolar concentrations of Cu2+ and Fe3+ ions on amyloid formation of selected ?-synuclein variants (wild-type and A53T ?-synuclein, in normal and N-terminally acetylated forms). As shown previously, Cu2+ speeds up aggregation of normal wild-type ?-synuclein, but not the acetylated form. However, Cu2+ has a minimal effect on (the faster) aggregation of normal A53T ?-synuclein, despite that Cu2+ binds to this variant. Like Cu2+, Fe3+ speeds up aggregation of non-acetylated wild-type ?-synuclein, but with acetylation, Fe3+ instead slows down aggregation. In contrast, for A53T ?-synuclein, regardless of acetylation, Fe3+ slows down aggregation with the effect being most dramatic for acetylated A53T ?-synuclein. The results presented here suggest a correlation between metal-ion modulation effect and intrinsic aggregation speed of the various ?-synuclein variants.

SUBMITTER: Lorentzon E

PROVIDER: S-EPMC7295844 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Differential effects of Cu2+ and Fe3+ ions on in vitro amyloid formation of biologically-relevant α-synuclein variants.

Lorentzon Emma E Kumar Ranjeet R Horvath Istvan I Wittung-Stafshede Pernilla P

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 20200313 2-3

Alterations in metal ion homeostasis appear coupled to neurodegenerative disorders but mechanisms are unknown. Amyloid formation of the protein α-synuclein in brain cells is a hallmark of Parkinson's disease. α-Synuclein can bind several metal ions in vitro and such interactions may affect the assembly process. Here we used biophysical methods to study the effects of micromolar concentrations of Cu2+ and Fe3+ ions on amyloid formation of selected α-synuclein variants (wild- ...[more]

PMID: 32170541

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Project description:Development of energetic catalysts with high energy density and strong catalytic activity has become the focus and frontier of research, which is expected to improve the combustion performance and ballistic properties of solid propellants. In this work, three energetic catalysts, M(H2O)4(AFCA)2·H2O (AFCA = 3-aminofurazan-4-carboxylic acid, M = Cu, Co, Fe), are designed and synthesized based on the coordination reaction of transition metal ions and the energetic ligand. The target products are characterized by single crystal X-ray diffraction, Fourier transform infrared spectroscopy, differential thermal analysis, optical microscopy, and scanning electron microscopy. The results reveal that Cu(H2O)4(AFCA)2·H2O crystallizes in the monoclinic space group, Dc = 1.918 g cm-3. Co(H2O)4(AFCA)2·H2O, and Fe(H2O)4(AFCA)2·H2O belong to orthorhombic space groups, their density is 1.886 g cm-3 and 1.856 g cm-3, respectively. In addition, the designed catalysts show higher catalytic activity than some reported catalysts such as Co(en)(H2BTI)2]2·en (H3BTI = 4,5-bis(1H-tetrazol-5-yl)-1H-imida-zole), Co-AzT (H2AzT = 5,5'-azotetrazole-1,1'-diol), and [Pb(BTF)(H2O)2]n (BTF = 4,4'-oxybis [3,3'-(1-hydroxy-tetrazolyl)]furazan) for the thermal decomposition of ammonium perchlorate (AP). The high-temperature decomposition peak temperatures of AP/Cu(H2O)4(AFCA)2·H2O, AP/Co(H2O)4(AFCA)2·H2O, and AP/Fe(H2O)4 (AFCA)2·H2O are decreased by 120.3 °C, 151.8 °C and 89.5 °C compared to the case of pure AP, while the heat release of them are increased by 768.8 J g-1, 780.5 J g-1, 750.9 J g-1, respectively. Moreover, the burning rates of solid propellants composed of AP/Cu(AFCA)2(H2O)4·H2O, AP/Co(AFCA)2(H2O)4·H2O and AP/Fe(AFCA)2(H2O)4·H2O are increased by 2.16 mm s-1, 2.53 mm s-1, and 1.57 mm s-1 compared with the case of pure AP. This research shows considerable application prospects in improving the combustion and energy performance of solid propellants, it is also a reference for the design and preparation of other novel energetic catalysts.

Dataset Information

Differential effects of Cu2+ and Fe3+ ions on in vitro amyloid formation of biologically-relevant ?-synuclein variants.

Publications

Differential effects of Cu<sup>2+</sup> and Fe<sup>3+</sup> ions on in vitro amyloid formation of biologically-relevant α-synuclein variants.

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