In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers.

ABSTRACT: Knowledge of the mechanisms of assembly of amyloid proteins into aggregates is of central importance in building an understanding of neurodegenerative disease. Given that oligomeric intermediates formed during the aggregation reaction are believed to be the major toxic species, methods to track such intermediates are clearly needed. Here we present a method, electron paramagnetic resonance (EPR), by which the amount of intermediates can be measured over the course of the aggregation, directly in the reacting solution, without the need for separation. We use this approach to investigate the aggregation of α-synuclein (αS), a synaptic protein implicated in Parkinson's disease and find a large population of oligomeric species. Our results show that these are primary oligomers, formed directly

SUBMITTER: Zurlo E 

PROVIDER: S-EPMC7822277 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature