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Bivalent metal ions induce formation of $\upalpha$-synuclein fibril polymorphs with different cytotoxicitiesстатья Исследовательская статья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Atarod Deyhim, Mamashli Fatemeh, Ghasemi Atiyeh, Moosavi-Movahedi Faezeh, Pirhaghi Mitra, Nedaei Hadi, Muronetz Vladimir, Haertlé Thomas, Tatzelt Jörg, Riazi Gholamhossein, Saboury Ali Akbar
- Журнал: Scientific reports
- Том: 12
- Номер: 1
- Год издания: 2022
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 1
- Последняя страница: 12
- Номер статьи: 11898
- DOI: 10.1038/s41598-022-15472-4
- Аннотация: α-Synuclein (α-Syn) aggregates are key components of intracellular inclusion bodies characteristic of Parkinson's disease (PD) and other synucleinopathies. Metal ions have been considered as the important etiological factors in PD since their interactions with α-Syn alter the kinetics of fibrillation. In the present study, we have systematically explored the effects of Zn2+, Cu2+, Ca2+, and Mg2+ cations on α-Syn fibril formation. Specifically, we determined fibrillation kinetics, size, morphology, and secondary structure of the fibrils and their cytotoxic activity. While all cations accelerate fibrillation, we observed distinct effects of the different ions. For example, Zn2+ induced fibrillation by lower tlag and higher kapp and formation of shorter fibrils, while Ca2+ ions lead to formation of longer fibrils, as evidenced by dynamic light scattering and atomic force microscopy studies. Additionally, the morphology of formed fibrils was different. Circular dichroism and attenuated total reflection-Fourier transform infrared spectroscopies revealed higher contents of β-sheets in fibrils. Interestingly, cell viability studies indicated nontoxicity of α-Syn fibrils formed in the presence of Zn2+ ions, while the fibrils formed in the presence of Cu2+, Ca2+, and Mg2+ were cytotoxic. Our results revealed that α-Syn fibrils formed in the presence of different divalent cations have distinct structural and cytotoxic features.
- Добавил в систему: Муронец Владимир Израилевич