α-Synuclein phosphorylation at serine 129 occurs after initial protein deposition and inhibits seeded fibril formation and toxicity | Zendy

Simona S. Ghanem | Zendy; Nour K. Majbour | Zendy; Nishant N. Vaikath | Zendy; Mustafa T. Ardah | Zendy; Daniel Erskine | Zendy; Nanna Møller Jensen | Zendy; Muneera Fayyad | Zendy; Indulekha P. Sudhakaran | Zendy; Eftychia Vasili | Zendy; Katerina Melachroinou | Zendy; Ilham Y. Abdi | Zendy; Ilaria Poggiolini | Zendy; Patrícia I. Santos | Zendy; Anton Emil Dorn | Zendy; Paolo Carloni | Zendy; Kostas Vekrellis | Zendy; Johannes Attems | Zendy; Ian G. McKeith | Zendy; Tiago F. Outeiro | Zendy; Poul Henning Jensen | Zendy; Omar M. A. ElAgnaf | Zendy

Open Access

α-Synuclein phosphorylation at serine 129 occurs after initial protein deposition and inhibits seeded fibril formation and toxicity

Author(s) -

Simona S. Ghanem,

Nour K. Majbour,

Nishant N. Vaikath,

Mustafa T. Ardah,

Daniel Erskine,

Nanna Møller Jensen,

Muneera Fayyad,

Indulekha P. Sudhakaran,

Eftychia Vasili,

Katerina Melachroinou,

Ilham Y. Abdi,

Ilaria Poggiolini,

Patrícia I. Santos,

Anton Emil Dorn,

Paolo Carloni,

Kostas Vekrellis,

Johannes Attems,

Ian G. McKeith,

Tiago F. Outeiro,

Poul Henning Jensen,

Omar M. A. ElAgnaf

Publication year - 2022

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2109617119

Subject(s) - phosphorylation , dementia with lewy bodies , fibril , toxicity , serine , chemistry , alpha synuclein , lewy body , protein aggregation , monoclonal antibody , neurotoxicity , microbiology and biotechnology , biochemistry , antibody , biophysics , parkinson's disease , biology , medicine , disease , pathology , dementia , immunology , organic chemistry

Significance Converging evidence points to the build-up of phosphorylated α-synuclein (α-syn) at residue serine 129 (pS129) in Lewy body disease, suggesting its central role in the regulation of α-syn aggregation and neuronal degeneration. However, a comprehensive understanding of the role of α-syn phosphorylation at pS129 in α-synuclenopathies pathogenesis is still lacking. Herein, we study the phosphorylation incidence and its effect on α-syn aggregation propensity and cellular toxicity. Collectively, our data suggest that pS129 occurred subsequent to initial α-syn aggregation, lessened aggregation propensity, and attenuated cytotoxicity through diverse assays. Our findings highlight major implications for a better understanding of the role of a molecular modification on protein aggregation.

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