α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells

Post-mortem analyses of brains from patients with Parkinson disease who received fetal mesencephalic transplants show that α-synuclein-containing (α-syn-containing) Lewy bodies gradually appear in grafted neurons. Here, we explored whether intercellular transfer of α-syn from host to graft, followed by seeding of α-syn aggregation in recipient neurons, can contribute to this phenomenon. We assessed α-syn cell-to-cell transfer using microscopy, flow cytometry, and high-content screening in several coculture model systems. Coculturing cells engineered to express either GFP- or DsRed-tagged α-syn resulted in a gradual increase in double-labeled cells. Importantly, α-syn-GFP derived from 1 neuroblastoma cell line…

• MJ
  Michael J. Fox Foundation for Parkinson's Research
• AN
  Agence Nationale de la Recherche
• KO
  Knut och Alice Wallenbergs Stiftelse
• V
  Vetenskapsrådet
• SL
  Stiftelsen Lars Hiertas Minne
• CN
  Centre National de la Recherche Scientifique
• P
  Parkinsonfonden