Amyloid protein‐induced sequestration of the eukaryotic ribosome: effect of stoichiometry and polyphenolic inhibitors

Abstract

Alzheimer's disease (AD) is characterized by the appearance of neurofibrillary tangles comprising of the Tau protein and aggregation of amyloid‐β peptides (Aβ 1–40 and Aβ 1–42). A concomitant loss of the ribosomal population is also observed in AD‐affected neurons. Our studies demonstrate that, similarly to Tau protein aggregation, in vitro aggregation of Aβ peptides in the vicinity of the yeast 80S ribosome can induce co‐aggregation of ribosomal components. The RNA‐stimulated aggregation of Aβ peptides and the Tau‐K18 variant is dependent on the RNA:protein stoichiometric ratio. A similar effect of stoichiometry is also observed on the ribosome–protein co‐aggregation process. Polyphenolic inhibitors of amyloid aggregation, such as rosmarinic acid and myricetin, inhibit RNA‐stimulated Aβ and Tau‐K18 aggregation and can mitigate the co‐aggregation of ribosomal components.