Open Accessα-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 Abdi,
Ilaria Poggiolini,
Patrícia Santos,
Anton Emil Dorn,
Paolo Carloni,
Kostas Vekrellis,
Johannes Attems,
Ian Mckeith,
Tiago F. Outeiro,
Poul Henning Jensen,
Omar M. A. ElAgnaf
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109617119
Subject(s) - phosphorylation , fibril , dementia with lewy bodies , toxicity , serine , chemistry , alpha synuclein , protein aggregation , lewy body , monoclonal antibody , biochemistry , microbiology and biotechnology , biophysics , antibody , biology , parkinson's disease , medicine , pathology , disease , immunology , dementia , 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.