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

ABSTRACT: The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-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 α-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 α-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. Identific

SUBMITTER: Lovestam S 

PROVIDER: S-EPMC8016116 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature