Seeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy

The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of alpha-synuclein into filaments is believed to underlie the prion-like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of alpha-synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human alpha-synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of the seeds. Identification of these factors will be essential for understanding the prion-like spreading of alpha-synuclein proteinopathies.

Automated summary

The study found that the structures of seeded assemblies differ from those of the seeds, indicating that additional unknown factors may play a role in the propagation of seeds. Identification of these factors is crucial for understanding the prion-like spreading of alpha-synuclein proteinopathies.