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

Alzheimer's disease (AD) is characterized by the appearance of neurofibrillary tangles comprising of the Tau protein and aggregation of amyloid-ß peptides (Aß 1-40 and Aß 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 Aß peptides in the vicinity of the yeast 80S ribosome can induce co-aggregation of ribosomal components. The RNA-stimulated aggregation of Aß 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 Aß and Tau-K18 aggregation and can mitigate the co-aggregation of ribosomal components.