Probing the Occurrence of Soluble Oligomers through Amyloid Aggregation Scaling Laws.

ABSTRACT: Drug discovery frequently relies on the kinetic analysis of physicochemical reactions that are at the origin of the disease state. Amyloid fibril formation has been extensively investigated in relation to prevalent and rare neurodegenerative diseases, but thus far no therapeutic solution has directly arisen from this knowledge. Other aggregation pathways producing smaller, hard-to-detect soluble oligomers are increasingly appointed as the main reason for cell toxicity and cell-to-cell transmissibility. Here we show that amyloid fibrillation kinetics can be used to unveil the protein oligomerization state. This is illustrated for human insulin and ataxin-3, two model proteins for which the amyloidogenic and oligomeric pathways are well characterized. Aggregation curves measured by the stand

SUBMITTER: Silva A 

PROVIDER: S-EPMC6316134 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature